311 lines
61 KiB
HTML
311 lines
61 KiB
HTML
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<rss xmlns:atom="http://www.w3.org/2005/Atom" version="2.0">
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<channel>
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<title>New GEO Series</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/</link>
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<atom:link href="http://www.ncbi.nlm.nih.gov/geo/feed/series/" rel="self" type="application/rss+xml"/>
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<description>GEO series published today</description>
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<pubDate>Wed, 05 Mar 2025 02:46:12 -0400</pubDate>
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<item>
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<title>GSE291109 Pcf11/Spt5 condensates stall RNA polymerase II to facilitate termination and piRNA-guided heterochromatin formation [chRNA]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291109</link>
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<guid isPermaLink="false">GSE291109</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Weiwei Liu ; Lijun Deng ; Ming Wang ; Xuan Ouyang ; Yang Yu<br><i>Series Type</i> : Other<br><i>Organism</i> : Drosophila melanogaster ; Mus musculus<p>The Piwi-interacting RNA (piRNA) pathway plays a crucial role in protecting animal germ cells by repressing transposons. However, the mechanism behind this RNA-mediated epigenetic regulation that leads to heterochromatin formation is not yet fully understood. Through RNA interference screens, we discovered Pcf11 and PNUTS, two conserved termination factors of RNA polymerase II (Pol II), as essential for piRNA-guided silencing. When Pcf11 is artificially tethered to a reporter, it leads to co-transcriptional repression and Pol II stalling, both of which are dependent on an alpha-helical region of Pcf11 capable of forming condensates when triggered by the C-terminal repeat domain (CTD) of Pol II. Interestingly, an intrinsically disordered region (IDR) derived from the Plant FCA can substitute for the alpha-helical region of Pcf11 in its silencing capacity and support animal development, demonstrating a causal relationship between phase separation and Pcf11’s function. Further exploration into how Pcf11 causes Pol II stalling revealed a direct interaction between Pcf11’s CTD-interaction domain (CID) and a CTR region of Spt5. The dephosphorylation of Spt5-CTR by PP1/PNUTS is essential for Pcf11’s recruitment during Pol II termination. It appears that the phosphorylated state of CTR inhibits Pcf11 condensate formation, while the phosphorylation of Pol II CTD at Threonine 4 enhances Pcf11’s ability to undergo phase separation. In conclusion, we propose a model in which Pcf11 regulates transcriptional termination by slowing down Pol II elongation, a process that is aided by phase separation with the unphosphorylated Spt5. The ability of Pcf11 to stall Pol II, utilized by the piRNA pathway to initiate heterochromatin formation, might represent a universal strategy for nascent RNA-mediated epigenetic control.</description>
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<category>Other</category>
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<category>Drosophila melanogaster</category>
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<category>Mus musculus</category>
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</item>
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<item>
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<title>GSE291108 Pcf11/Spt5 condensates stall RNA polymerase II to facilitate termination and piRNA-guided heterochromatin formation [PRO-Seq]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291108</link>
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<guid isPermaLink="false">GSE291108</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Weiwei Liu ; Lijun Deng ; Ming Wang ; Xuan Ouyang ; Yang Yu<br><i>Series Type</i> : Other<br><i>Organism</i> : Drosophila melanogaster ; Mus musculus<p>The Piwi-interacting RNA (piRNA) pathway plays a crucial role in protecting animal germ cells by repressing transposons. However, the mechanism behind this RNA-mediated epigenetic regulation that leads to heterochromatin formation is not yet fully understood. Through RNA interference screens, we discovered Pcf11 and PNUTS, two conserved termination factors of RNA polymerase II (Pol II), as essential for piRNA-guided silencing. When Pcf11 is artificially tethered to a reporter, it leads to co-transcriptional repression and Pol II stalling, both of which are dependent on an alpha-helical region of Pcf11 capable of forming condensates when triggered by the C-terminal repeat domain (CTD) of Pol II. Interestingly, an intrinsically disordered region (IDR) derived from the Plant FCA can substitute for the alpha-helical region of Pcf11 in its silencing capacity and support animal development, demonstrating a causal relationship between phase separation and Pcf11’s function. Further exploration into how Pcf11 causes Pol II stalling revealed a direct interaction between Pcf11’s CTD-interaction domain (CID) and a CTR region of Spt5. The dephosphorylation of Spt5-CTR by PP1/PNUTS is essential for Pcf11’s recruitment during Pol II termination. It appears that the phosphorylated state of CTR inhibits Pcf11 condensate formation, while the phosphorylation of Pol II CTD at Threonine 4 enhances Pcf11’s ability to undergo phase separation. In conclusion, we propose a model in which Pcf11 regulates transcriptional termination by slowing down Pol II elongation, a process that is aided by phase separation with the unphosphorylated Spt5. The ability of Pcf11 to stall Pol II, utilized by the piRNA pathway to initiate heterochromatin formation, might represent a universal strategy for nascent RNA-mediated epigenetic control.</description>
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<category>Other</category>
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<category>Drosophila melanogaster</category>
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<category>Mus musculus</category>
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</item>
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<item>
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<title>GSE291105 Pcf11/Spt5 condensates stall RNA polymerase II to facilitate termination and piRNA-guided heterochromatin formation [ChIP-Seq]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291105</link>
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<guid isPermaLink="false">GSE291105</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Weiwei Liu ; Lijun Deng ; Ming Wang ; Xuan Ouyang ; Yang Yu<br><i>Series Type</i> : Genome binding/occupancy profiling by high throughput sequencing<br><i>Organism</i> : Drosophila melanogaster ; Mus musculus<p>The Piwi-interacting RNA (piRNA) pathway plays a crucial role in protecting animal germ cells by repressing transposons. However, the mechanism behind this RNA-mediated epigenetic regulation that leads to heterochromatin formation is not yet fully understood. Through RNA interference screens, we discovered Pcf11 and PNUTS, two conserved termination factors of RNA polymerase II (Pol II), as essential for piRNA-guided silencing. When Pcf11 is artificially tethered to a reporter, it leads to co-transcriptional repression and Pol II stalling, both of which are dependent on an alpha-helical region of Pcf11 capable of forming condensates when triggered by the C-terminal repeat domain (CTD) of Pol II. Interestingly, an intrinsically disordered region (IDR) derived from the Plant FCA can substitute for the alpha-helical region of Pcf11 in its silencing capacity and support animal development, demonstrating a causal relationship between phase separation and Pcf11’s function. Further exploration into how Pcf11 causes Pol II stalling revealed a direct interaction between Pcf11’s CTD-interaction domain (CID) and a CTR region of Spt5. The dephosphorylation of Spt5-CTR by PP1/PNUTS is essential for Pcf11’s recruitment during Pol II termination. It appears that the phosphorylated state of CTR inhibits Pcf11 condensate formation, while the phosphorylation of Pol II CTD at Threonine 4 enhances Pcf11’s ability to undergo phase separation. In conclusion, we propose a model in which Pcf11 regulates transcriptional termination by slowing down Pol II elongation, a process that is aided by phase separation with the unphosphorylated Spt5. The ability of Pcf11 to stall Pol II, utilized by the piRNA pathway to initiate heterochromatin formation, might represent a universal strategy for nascent RNA-mediated epigenetic control.</description>
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<category>Genome binding/occupancy profiling by high throughput sequencing</category>
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<category>Drosophila melanogaster</category>
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<category>Mus musculus</category>
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</item>
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<item>
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<title>GSE291104 Pcf11/Spt5 condensates stall RNA polymerase II to facilitate termination and piRNA-guided heterochromatin formation [CUT&Tag]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291104</link>
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<guid isPermaLink="false">GSE291104</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Weiwei Liu ; Lijun Deng ; Ming Wang ; Xuan Ouyang ; Yang Yu<br><i>Series Type</i> : Genome binding/occupancy profiling by high throughput sequencing<br><i>Organism</i> : Mus musculus<p>The Piwi-interacting RNA (piRNA) pathway plays a crucial role in protecting animal germ cells by repressing transposons. However, the mechanism behind this RNA-mediated epigenetic regulation that leads to heterochromatin formation is not yet fully understood. Through RNA interference screens, we discovered Pcf11 and PNUTS, two conserved termination factors of RNA polymerase II (Pol II), as essential for piRNA-guided silencing. When Pcf11 is artificially tethered to a reporter, it leads to co-transcriptional repression and Pol II stalling, both of which are dependent on an alpha-helical region of Pcf11 capable of forming condensates when triggered by the C-terminal repeat domain (CTD) of Pol II. Interestingly, an intrinsically disordered region (IDR) derived from the Plant FCA can substitute for the alpha-helical region of Pcf11 in its silencing capacity and support animal development, demonstrating a causal relationship between phase separation and Pcf11’s function. Further exploration into how Pcf11 causes Pol II stalling revealed a direct interaction between Pcf11’s CTD-interaction domain (CID) and a CTR region of Spt5. The dephosphorylation of Spt5-CTR by PP1/PNUTS is essential for Pcf11’s recruitment during Pol II termination. It appears that the phosphorylated state of CTR inhibits Pcf11 condensate formation, while the phosphorylation of Pol II CTD at Threonine 4 enhances Pcf11’s ability to undergo phase separation. In conclusion, we propose a model in which Pcf11 regulates transcriptional termination by slowing down Pol II elongation, a process that is aided by phase separation with the unphosphorylated Spt5. The ability of Pcf11 to stall Pol II, utilized by the piRNA pathway to initiate heterochromatin formation, might represent a universal strategy for nascent RNA-mediated epigenetic control.</description>
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<category>Genome binding/occupancy profiling by high throughput sequencing</category>
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<category>Mus musculus</category>
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</item>
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<item>
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<title>GSE291080 Clonal cell states link gastroesophageal junction tissues, metaplasia, and cancer [scRNA-seq]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291080</link>
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<guid isPermaLink="false">GSE291080</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Rodrigo A Gier ; Raúl A Reyes Hueros ; Jiazhen Rong ; Maureen DeMarshall ; Sydney A Bracht ; Tatiana A Karakasheva ; Amanda B Muir ; Gary W Falk ; Nancy R Zhang ; Sydney M Shaffer<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Barrett's esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett’s esophagus have not been resolved in humans. Here, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis unexpectedly revealed that the squamous esophagus and gastric cardia contained cells belonging to common lineages that also included transitional basal progenitor cells; both esophageal and gastric tissues were also related to Barrett's esophagus. Barrett’s esophagus biopsies consisted of multiple clones, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic lesions were initiated by the expansion of a single molecularly aberrant Barrett’s esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett's esophagus, linking cell states along the disease trajectory, from its origin to cancer.</description>
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<category>Expression profiling by high throughput sequencing</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE291036 TP53 missense-specific transcriptional plasticity drives resistance against cell cycle inhibitors in pancreatic cancer</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291036</link>
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<guid isPermaLink="false">GSE291036</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Series Type</i> : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>This SuperSeries is composed of the SubSeries listed below.</description>
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<category>Expression profiling by high throughput sequencing</category>
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<category>Genome binding/occupancy profiling by high throughput sequencing</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE291035 TP53 missense-specific transcriptional plasticity drives resistance against cell cycle inhibitors in pancreatic cancer [ChIP-Seq]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291035</link>
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<guid isPermaLink="false">GSE291035</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Laura Urbach ; Lena Wieland ; Frederike Penz ; Stefan Küffer ; Rebecca D Samuel ; Lukas Klein ; Christof Lenz ; Ulrich Sax ; Michael Ghadimi ; Ramona Schulz-Heddergott ; Elisabeth Hessmann ; Volker Ellenrieder ; Nelson Dusetti ; Shiv K Singh<br><i>Series Type</i> : Genome binding/occupancy profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>In ~70% of pancreatic ductal adenocarcinoma (PDAC) patients, the TP53 gene acquires gain-of-function (GOF) mutations leading to rapid disease progression. Specifically, missense p53 (misp53) GOF mutations associate with therapy resistance and worse clinical outcomes. However, the molecular functions of distinct misp53 mutants in plasticity and therapy response remain unclear. Integrating multi-center patients’ data and multi-omics, we report that the misp53R273H/C mutant is associated with cell-cycle progression and a basal-like state compared to the misp53R248W/Q mutant. Loss of misp53R273H/C decreased tumor growth and liver metastasis while prolonging survival in preclinical models. We found that misp53R273H/C specifically regulates the Rb/DREAM axis involved in cell cycle regulation. Notably, a clinical CDK4/6 inhibitor specifically reduced misp53R273H/C mutant expression. However, it triggered MAPK/ERK-mediated resistance mechanisms, enhancing cell survival and resistance to CDK4/6 inhibitors. Combining MAPK/ERK and CDK4/6 inhibitors reduced misp53R273H/C-associated oncogenic functions. Thus, distinct misp53 mutants show unique cell-intrinsic plasticity, therapeutic vulnerabilities, and resistance mechanisms.</description>
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<category>Genome binding/occupancy profiling by high throughput sequencing</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE291033 TP53 missense-specific transcriptional plasticity drives resistance against cell cycle inhibitors in pancreatic cancer [RNA-Seq]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291033</link>
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<guid isPermaLink="false">GSE291033</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Laura Urbach ; Lena Wieland ; Frederike Penz ; Stefan Küffer ; Rebecca D Samuel ; Lukas Klein ; Christof Lenz ; Ulrich Sax ; Michael Ghadimi ; Ramona Schulz-Heddergott ; Elisabeth Hessmann ; Volker Ellenrieder ; Nelson Dusetti ; Shiv K Singh<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>In ~70% of pancreatic ductal adenocarcinoma (PDAC) patients, the TP53 gene acquires gain-of-function (GOF) mutations leading to rapid disease progression. Specifically, missense p53 (misp53) GOF mutations associate with therapy resistance and worse clinical outcomes. However, the molecular functions of distinct misp53 mutants in plasticity and therapy response remain unclear. Integrating multi-center patients’ data and multi-omics, we report that the misp53R273H/C mutant is associated with cell-cycle progression and a basal-like state compared to the misp53R248W/Q mutant. Loss of misp53R273H/C decreased tumor growth and liver metastasis while prolonging survival in preclinical models. We found that misp53R273H/C specifically regulates the Rb/DREAM axis involved in cell cycle regulation. Notably, a clinical CDK4/6 inhibitor specifically reduced misp53R273H/C mutant expression. However, it triggered MAPK/ERK-mediated resistance mechanisms, enhancing cell survival and resistance to CDK4/6 inhibitors. Combining MAPK/ERK and CDK4/6 inhibitors reduced misp53R273H/C-associated oncogenic functions. Thus, distinct misp53 mutants show unique cell-intrinsic plasticity, therapeutic vulnerabilities, and resistance mechanisms.</description>
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<category>Expression profiling by high throughput sequencing</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE291013 Methylation pseudotime analysis for label-free profiling of the temporal chromatin landscape with long-read and single-molecule resolution</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291013</link>
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<guid isPermaLink="false">GSE291013</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Series Type</i> : Genome binding/occupancy profiling by high throughput sequencing ; Other<br><i>Organism</i> : Homo sapiens<p>This SuperSeries is composed of the SubSeries listed below.</description>
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<category>Genome binding/occupancy profiling by high throughput sequencing</category>
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<category>Other</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE290978 Methylation pseudotime analysis for label-free profiling of the temporal chromatin landscape with long-read and single-molecule resolution [Nanopore]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290978</link>
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<guid isPermaLink="false">GSE290978</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Annie Trinh ; Navied Akhtar ; Kwadwo Bonsu ; Nandor Laszik ; Asia Mendelevich ; Tanye Wen ; Julien L P Morival ; Katelyn Diune ; Mitchell P Frazeur ; Justin Vega ; Alexander A Gimelbrant ; Elizabeth L Read ; Timothy L Downing<br><i>Series Type</i> : Other<br><i>Organism</i> : Homo sapiens<p>Faithful epigenetic inheritance across cell divisions is essential to maintaining cell identity and involves numerous epigenetic modifications, whose roles in coordinating chromatin architecture are less understood. Technological approaches to temporally order epigenetic modifications throughout the cell cycle often face limitations in sequence resolution and rely on potentially damaging mitotic labeling or conversion steps. Herein, we present Methylation Pseudotime Analysis Through read-level Heterogeneity (MPATH), a label- and conversion-free method to infer post-replication DNA strand maturity from methylation patterns across single molecules. We use MPATH to temporally order hydroxymethylation throughout mitotic inheritance revealing, for the first time, that CpGs within cis-regulatory elements undergo transitions between methylation states at sub-cell-cycle timescales. When applied to long reads generated by NOMe-seq, MPATH uncovered relationships between nucleosome occupancy and DNA maturity. Finally, extension of MPATH to phased reads reveals allele-specific trends in pseudotime distribution associated with X chromosome inactivation. Our findings suggest that when coupled with multimodal sequencing strategies, MPATH could provide valuable insights into chromatin restoration dynamics.</description>
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<category>Other</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE290974 Methylation pseudotime analysis for label-free profiling of the temporal chromatin landscape with long-read and single-molecule resolution [ATAC-seq]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290974</link>
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<guid isPermaLink="false">GSE290974</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Annie Trinh ; Navied Akhtar ; Kwadwo Bonsu ; Nandor Laszik ; Asia Mendelevich ; Tanye Wen ; Julien L P Morival ; Katelyn Diune ; Mitchell P Frazeur ; Justin Vega ; Alexander A Gimelbrant ; Elizabeth L Read ; Timothy L Downing<br><i>Series Type</i> : Genome binding/occupancy profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Faithful epigenetic inheritance across cell divisions is essential to maintaining cell identity and involves numerous epigenetic modifications, whose roles in coordinating chromatin architecture are less understood. Technological approaches to temporally order epigenetic modifications throughout the cell cycle often face limitations in sequence resolution and rely on potentially damaging mitotic labeling or conversion steps. Herein, we present Methylation Pseudotime Analysis Through read-level Heterogeneity (MPATH), a label- and conversion-free method to infer post-replication DNA strand maturity from methylation patterns across single molecules. We use MPATH to temporally order hydroxymethylation throughout mitotic inheritance revealing, for the first time, that CpGs within cis-regulatory elements undergo transitions between methylation states at sub-cell-cycle timescales. When applied to long reads generated by NOMe-seq, MPATH uncovered relationships between nucleosome occupancy and DNA maturity. Finally, extension of MPATH to phased reads reveals allele-specific trends in pseudotime distribution associated with X chromosome inactivation. Our findings suggest that when coupled with multimodal sequencing strategies, MPATH could provide valuable insights into chromatin restoration dynamics.</description>
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<category>Genome binding/occupancy profiling by high throughput sequencing</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE290845 Cancer-Associated Fibroblasts Shape a High-Lactate Microenvironment to Drive Perineural Invasion in Pancreatic Cancer via Histone Lactylation [RNA-seq]</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290845</link>
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<guid isPermaLink="false">GSE290845</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Tingting Li ; Chonghui Hu ; Tianhao Huang ; Yu Zhou<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Perineural invasion (PNI) is a pivotal prognostic factor in pancreatic cancer, associated with aggressive tumor behavior and adverse patient outcomes. Despite its recognized clinical impact, the molecular mechanisms underlying PNI are not well understood. In this study, we isolated perineural invasion-associated cancer-associated fibroblasts (pCAFs), which demonstrated a markedly enhanced capacity to promote neural invasion in pancreatic cancer compared to non-perineural invasion-associated CAFs (npCAFs). Utilizing single-cell, high-throughput sequencing, and metabolomics, we identified a significant upregulation of glycolysis in pCAFs, fostering a high-lactate tumor microenvironment conducive to cancer progression. pCAFs-derived lactate is absorbed by tumor cells, facilitating histone H3K18 lactylation. This epigenetic modification activates the transcription of neural invasion-associated genes such as L1CAM and SLIT1, thereby driving PNI in pancreatic cancer. Further exploration of metabolic reprogramming in pCAFs revealed enhanced acetylation of the glycolytic enzyme GAPDH, correlated with increased enzymatic activity and glycolytic flux. Targeting of GAPDH and lactylation modifications significantly inhibits neural invasion in a KPC mouse model. Clinical data suggested that high levels of H3K18 lactylation correlate with severe PNI and poorer patient prognosis. Our findings provide critical insights into the role of pCAFs in the PNI of pancreatic cancer, highlighting glycolytic reprogramming and lactate-driven histone modifications as potential therapeutic targets for PDAC.</description>
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<category>Expression profiling by high throughput sequencing</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE290844 The role of TRAF1 in Helicobacter pylori infection</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290844</link>
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<guid isPermaLink="false">GSE290844</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Fen Wang ; Lingzhi Yuan<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Our previous study has found the VacA virulence of Helicobacter pylori could induce the apoptosis of gastric epithelial cells and TRAF1 plays a crucial role in this process. In order to further investigate the detailed mechanism of TRAF1-related apoptosis, we constructed a TRAF1 knockdown model in MKN74 cells and TRAF1 overexpressing model in HGC27 cells.</description>
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<category>Expression profiling by high throughput sequencing</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE290821 Interleukin-4 Antagonizes Inflammation and Aging Caused Hematopoiesis Dysregulation</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290821</link>
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<guid isPermaLink="false">GSE290821</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributor</i> : Jingfei Yao<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Mus musculus<p>IL-4, not only drives Th2 cell differentiation and reprogram macrophages toward an anti-inflammatory state but also plays crucial roles in aging and immunotherapy. However, the role of IL-4-STAT6 signaling in hematopoietic stem and progenitor cells (HSPCs) are less studied. So we sequenced mRNA from IL-4-treated or STAT6-KO HSPCs, LT-HSCs and MPPs, to address the roles of IL-4-STAT6 signaling in hematopoiesis.</description>
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<category>Expression profiling by high throughput sequencing</category>
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<category>Mus musculus</category>
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</item>
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<item>
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<title>GSE290577 Dynamic responses to rejection in the transplanted human heart revealed through spatial transcriptomics</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290577</link>
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<guid isPermaLink="false">GSE290577</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Kaushik Amancherla ; Angela M Taravella Oill ; Xavier Bledsoe ; Arianna Williams ; Nelson Chow ; Shilin Zhao ; Quanhu Sheng ; David W Bearl ; Robert D Hoffman ; Jonathan N Menachem ; Hasan K Siddiqi ; Douglas M Brinkley ; Evan D Mee ; Niran Hadad ; Vineet Agrawal ; Jeffrey Schmeckpepper ; Aniket Rali ; Stacy Tsai ; Eric Farber-Eger ; Quinn S Wells ; Jane E Freedman ; Nathan R Tucker ; Kelly H Schlendorf ; Eric R Gamazon ; Ravi V Shah ; Nicholas Banovich<br><i>Series Type</i> : Other<br><i>Organism</i> : Homo sapiens<p>Allograft rejection following solid-organ transplantation is a major cause of graft dysfunction and mortality. Current approaches to diagnosis rely on histology, which exhibits wide diagnostic variability and lacks access to molecular phenotypes that may stratify therapeutic response. Here, we leverage image-based spatial transcriptomics at sub-cellular resolution in longitudinal human cardiac biopsies to characterize transcriptional heterogeneity in 62 adult and pediatric heart transplant (HT) recipients during and following histologically-diagnosed rejection. Across 28 cell types, we identified significant differences in abundance in CD4+ and CD8+ T cells, fibroblasts, and endothelial cells across different biological classes of rejection (cellular, mixed, antibody-mediated). We observed a broad overlap in cellular transcriptional states across histologic rejection severity and biological class and significant heterogeneity within rejection severity grades that would qualify for immunomodulatory treatment. Individuals who had resolved rejection after therapy had a distinct transcriptomic profile relative to those with persistent rejection, including 216 genes across 6 cell types along pathways of inflammation, IL6-JAK-STAT3 signaling, IFNα/IFNγ response, and TNFα signaling. Spatial transcriptomics also identified genes linked to long-term prognostic outcomes post-HT. These results underscore importance of subtyping immunologic states during rejection to stratify immune-cardiac interactions following HT that are therapeutically relevant to short- and long-term rejection-related outcomes.</description>
|
||
<category>Other</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE290519 Dexamethasone drives macrophage repolarization linked to increased triple-negative breast cancer aggressiveness</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290519</link>
|
||
<guid isPermaLink="false">GSE290519</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Mohamed M Shamekh ; Birgitta Lindqvist ; Ivan Nalvarte<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Glucocorticoids (GCs) are known for their anti-inflammatory potential, which includes macrophage polarization into an anti-inflammatory and tissue remodeling state. GCs are routinely co-administered to cancer patients to alleviate the side effects of chemotherapy. However, it is not well known if GCs can modulate tumor-associated macrophages (TAMs) to promote tumor progression. Here, we show that dexamethasone (DEX) induces dose-dependent differentiation of THP-1 monocyte-derived anti-tumorigenic (M1) macrophages into pro-tumorigenic (M2-like) macrophages, even in the presence of M1 cues, and that DEX can repolarize fully differentiated M1 macrophages into an M2-like state. These macrophages have a cytokine profile similar to the pro-tumorigenic (M2) macrophages and can stimulate the proliferation and invasion of triple-negative breast cancer (TNBC) cells in vitro. DEX treatment of an orthotopic mouse model of TNBC attenuated paclitaxel-mediated tumor growth inhibition, increased M2-like TAMs in primary tumors, and enhanced lung metastasis. Transcriptomic analysis of DEX-treated M1 macrophages revealed not only transcriptomic overlap to M2 macrophages, but to human breast cancer TAM transcriptomic data and further to a specific TAM signature associated with aggressive estrogen receptor-negative breast cancer. Our study illustrates a remarkable macrophage repolarization plasticity upon DEX exposure and warrants care in prescribing high doses of GCs to breast cancer patients, especially to those considered for chemotherapy.</description>
|
||
<category>Expression profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE288881 Phenotypic complexities of rare heterozygous neurexin-1 deletions [shNEG_ASO_rnaseq]</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288881</link>
|
||
<guid isPermaLink="false">GSE288881</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Michael B Fernando ; Yu Fan ; Yanchun Zhang ; Alex Tokolyi ; Aleta N Murphy ; Sarah K Kammourh ; Peter M Deans ; Sadaf Ghorbani ; Ryan Onatzevitch ; Adriana Pero ; Christopher Padilla ; Sarah Williams ; Erin K Flaherty ; Iya A Prytkova ; Lei Cao ; David A Knowles ; Gang Fang ; Paul A Slesinger ; Kristen J Brennand<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Given the large number of genes significantly associated with risk for neuropsychiatric disorders, a critical unanswered question is the extent to which diverse mutations --sometimes impacting the same gene-- will require tailored therapeutic strategies. Here we consider this in the context of rare neuropsychiatric disorder-associated copy number variants (2p16.3) resulting in heterozygous deletions in NRXN1, a pre-synaptic cell adhesion protein that serves as a critical synaptic organizer in the brain. Complex patterns of NRXN1 alternative splicing are fundamental to establishing diverse neurocircuitry, vary between the cell types of the brain, and are differentially impacted by unique (non-recurrent) deletions. We contrast the cell-type-specific impact of patient-specific mutations in NRXN1 using human induced pluripotent stem cells, finding that perturbations in NRXN1 splicing result in divergent cell-type-specific synaptic outcomes. Via distinct loss-of-function (LOF) and gain-of-function (GOF) mechanisms, NRXN1+/- deletions cause decreased synaptic activity in glutamatergic neurons, yet increased synaptic activity in GABAergic neurons. Reciprocal isogenic manipulations causally demonstrate that aberrant splicing drives these changes in synaptic activity. For NRXN1 deletions, and perhaps more broadly, precision medicine will require stratifying patients based on whether their gene mutations act through LOF or GOF mechanisms, in order to achieve individualized restoration of NRXN1 isoform repertoires by increasing wildtype, or ablating mutant isoforms. Given the increasing number of mutations predicted to engender both LOF and GOF mechanisms in brain disorders, our findings add nuance to future considerations of precision medicine.</description>
|
||
<category>Expression profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE288880 Phenotypic complexities of rare heterozygous neurexin-1 deletions [nrxn1_bulk_rnaseq]</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE288880</link>
|
||
<guid isPermaLink="false">GSE288880</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Michael B Fernando ; Yu Fan ; Yanchun Zhang ; Alex Tokolyi ; Aleta N Murphy ; Sarah K Kammourh ; Peter M Deans ; Sadaf Ghorbani ; Ryan Onatzevitch ; Adriana Pero ; Christopher Padilla ; Sarah Williams ; Erin K Flaherty ; Iya A Prytkova ; Lei Cao ; David A Knowles ; Gang Fang ; Paul A Slesinger ; Kristen J Brennand<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Given the large number of genes significantly associated with risk for neuropsychiatric disorders, a critical unanswered question is the extent to which diverse mutations --sometimes impacting the same gene-- will require tailored therapeutic strategies. Here we consider this in the context of rare neuropsychiatric disorder-associated copy number variants (2p16.3) resulting in heterozygous deletions in NRXN1, a pre-synaptic cell adhesion protein that serves as a critical synaptic organizer in the brain. Complex patterns of NRXN1 alternative splicing are fundamental to establishing diverse neurocircuitry, vary between the cell types of the brain, and are differentially impacted by unique (non-recurrent) deletions. We contrast the cell-type-specific impact of patient-specific mutations in NRXN1 using human induced pluripotent stem cells, finding that perturbations in NRXN1 splicing result in divergent cell-type-specific synaptic outcomes. Via distinct loss-of-function (LOF) and gain-of-function (GOF) mechanisms, NRXN1+/- deletions cause decreased synaptic activity in glutamatergic neurons, yet increased synaptic activity in GABAergic neurons. Reciprocal isogenic manipulations causally demonstrate that aberrant splicing drives these changes in synaptic activity. For NRXN1 deletions, and perhaps more broadly, precision medicine will require stratifying patients based on whether their gene mutations act through LOF or GOF mechanisms, in order to achieve individualized restoration of NRXN1 isoform repertoires by increasing wildtype, or ablating mutant isoforms. Given the increasing number of mutations predicted to engender both LOF and GOF mechanisms in brain disorders, our findings add nuance to future considerations of precision medicine.</description>
|
||
<category>Expression profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE285902 IL-15 complex enhances agonistic anti-CD40 + anti-PDL1 by correcting the T-bet to Tox ratio in CD8 T cells infiltrating pancreatic ductal adenocarcinoma</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285902</link>
|
||
<guid isPermaLink="false">GSE285902</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributor</i> : Ingunn M Stromnes<br><i>Series Type</i> : Expression profiling by high throughput sequencing ; Other<br><i>Organism</i> : Mus musculus<p>Single cell RNA sequencing paired with single cell V(D)J sequenction of immune cells infiltrating orthotopic KPC2a tumors, spleen cells, and CD8 T cells enriched from spleen cells on day 14 posttumor. Cohorts received no treatment, agonistic anti-CD40, anti-PD-L1 or the combination of agonistic anti-CD40 + anti-PDL1. Treatments were initated on day 7 posttumor.</description>
|
||
<category>Expression profiling by high throughput sequencing</category>
|
||
<category>Other</category>
|
||
<category>Mus musculus</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE285332 Spatial control of m6A deposition on enhancer and promoter RNAs by H3K27ac coordinated interaction between METTL3 and METTL14 [CUT&Tag]</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285332</link>
|
||
<guid isPermaLink="false">GSE285332</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Xiang Huang ; Jinkai Wang ; Zhijun Ren ; Meijun Ye<br><i>Series Type</i> : Genome binding/occupancy profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Interaction between the m6A methyltransferase METTL3 and METTL14 is critical for METTL3 to deposit m6A on various types of RNAs. It is still intriguing whether there is spatial control of m6A deposition on different types of RNAs. Here, through genome-wide CRISPR/Cas9 screening, we find H3K27ac acetylase p300-mediated METTL3 acetylation suppresses the binding of METTL3 on H3K27ac-marked chromatin by inhibiting its interaction with METTL14. Consistently, p300 catalyzing the acetylation of METTL3 specifically occurs on H3K27ac marked chromatin. Disruptive mutations on METTL3 acetylation sites selectively promote the m6A of chromatin-associated RNAs from p300-bound enhancers and promoters marked by H3K27ac, resulting in transcription inhibition of ferroptosis-inhibition related genes. In addition, PAK2 promotes METTL3 acetylation by phosphorylating METTL3. Inhibition of PAK2 promotes the ferroptosis in a manner that depends on the acetylation of METTL3. Our study reveals a spatial-selective way to specifically regulate the deposition of m6A on enhancer and promoter RNAs.</description>
|
||
<category>Genome binding/occupancy profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE285328 Spatial control of m6A deposition on enhancer and promoter RNAs by H3K27ac coordinated interaction between METTL3 and METTL14 [RNA-seq]</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285328</link>
|
||
<guid isPermaLink="false">GSE285328</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Xiang Huang ; Jinkai Wang ; Zhijun Ren ; Meijun Ye<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Interaction between the m6A methyltransferase METTL3 and METTL14 is critical for METTL3 to deposit m6A on various types of RNAs. It is still intriguing whether there is spatial control of m6A deposition on different types of RNAs. Here, through genome-wide CRISPR/Cas9 screening, we find H3K27ac acetylase p300-mediated METTL3 acetylation suppresses the binding of METTL3 on H3K27ac-marked chromatin by inhibiting its interaction with METTL14. Consistently, p300 catalyzing the acetylation of METTL3 specifically occurs on H3K27ac marked chromatin. Disruptive mutations on METTL3 acetylation sites selectively promote the m6A of chromatin-associated RNAs from p300-bound enhancers and promoters marked by H3K27ac, resulting in transcription inhibition of ferroptosis-inhibition related genes. In addition, PAK2 promotes METTL3 acetylation by phosphorylating METTL3. Inhibition of PAK2 promotes the ferroptosis in a manner that depends on the acetylation of METTL3. Our study reveals a spatial-selective way to specifically regulate the deposition of m6A on enhancer and promoter RNAs.</description>
|
||
<category>Expression profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE285327 Spatial control of m6A deposition on enhancer and promoter RNAs by H3K27ac coordinated interaction between METTL3 and METTL14 [caRNA-seq]</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE285327</link>
|
||
<guid isPermaLink="false">GSE285327</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Xiang Huang ; Jinkai Wang ; Zhijun Ren ; Meijun Ye<br><i>Series Type</i> : Other ; Non-coding RNA profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Interaction between the m6A methyltransferase METTL3 and METTL14 is critical for METTL3 to deposit m6A on various types of RNAs. It is still intriguing whether there is spatial control of m6A deposition on different types of RNAs. Here, through genome-wide CRISPR/Cas9 screening, we find H3K27ac acetylase p300-mediated METTL3 acetylation suppresses the binding of METTL3 on H3K27ac-marked chromatin by inhibiting its interaction with METTL14. Consistently, p300 catalyzing the acetylation of METTL3 specifically occurs on H3K27ac marked chromatin. Disruptive mutations on METTL3 acetylation sites selectively promote the m6A of chromatin-associated RNAs from p300-bound enhancers and promoters marked by H3K27ac, resulting in transcription inhibition of ferroptosis-inhibition related genes. In addition, PAK2 promotes METTL3 acetylation by phosphorylating METTL3. Inhibition of PAK2 promotes the ferroptosis in a manner that depends on the acetylation of METTL3. Our study reveals a spatial-selective way to specifically regulate the deposition of m6A on enhancer and promoter RNAs.</description>
|
||
<category>Other</category>
|
||
<category>Non-coding RNA profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE282274 Bulk RNA-seq of HFF cell senescence model induced by oncogene activation</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282274</link>
|
||
<guid isPermaLink="false">GSE282274</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>To investiage the mechanism of cellular senescence, we established a model of oncogene RAS-induced cellular senescence in human foreskin fibroblasts (HFF cells). We transduced an estrogen receptor fused to the H-RASG12V protein (ER:RAS) in HFF, which can be induced by 4-hydroxytamoxifen (4-OHT).</description>
|
||
<category>Expression profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE278536 ADAT3 variants disrupt the activity of the ADAT tRNA deaminase complex and impair neuronal migration.</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278536</link>
|
||
<guid isPermaLink="false">GSE278536</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Till Balla ; Danny D Nedialkova ; Juliette Godin<br><i>Series Type</i> : Other<br><i>Organism</i> : Homo sapiens<p>The ADAT2/ADAT3 (ADAT) complex catalyzes the adenosine to inosine modification at the wobble position of eukaryotic tRNAs. Mutations in ADAT3, the catalytically inactive subunit of the ADAT2/ADAT3 complex, have been identified in patients presenting with severe neurodevelopmental disorders. Yet, the physiological function of ADAT2/ADAT3 complex during brain development remains totally unknown. Here, we investigated the role of the ADAT2/ADAT3 complex in cortical development. First, we reported 21 new neurodevelopmental disorders patients carrying biallelic variants in ADAT3. Second, we used structural, biochemical, and enzymatic assays to deeply characterized the impact of those variants on ADAT2/ADAT3 structure, biochemical properties, enzymatic activity and tRNAs editing and abundance. Finally, in vivo complementation assays were performed to correlate functional deficits with neuronal migration defects in the developing mouse cortex. Our results showed that maintaining a proper level of ADAT2/ADAT3 catalytic activity is essential for radial migration of projection neurons in the developing mouse cortex. We demonstrated that the identified ADAT3 variants significantly impaired the abundance and, for some, the activity of the complex, leading to a substantial decrease in I34 levels with direct consequence on their steady-state. We correlated the severity of the migration phenotype with the degree of the loss of function caused by the variants. Altogether, our results highlight the critical role of ADAT2/ADAT3 during cortical development and provide cellular and molecular insights into the pathogenic mechanisms underlying ADAT3-related neurodevelopmental disorders.</description>
|
||
<category>Other</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE272469 Spatial control of m6A deposition on enhancer and promoter RNAs by H3K27ac coordinated interaction between METTL3 and METTL14</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272469</link>
|
||
<guid isPermaLink="false">GSE272469</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Series Type</i> : Expression profiling by high throughput sequencing ; Other ; Non-coding RNA profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing ; Methylation profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>This SuperSeries is composed of the SubSeries listed below.</description>
|
||
<category>Expression profiling by high throughput sequencing</category>
|
||
<category>Other</category>
|
||
<category>Non-coding RNA profiling by high throughput sequencing</category>
|
||
<category>Genome binding/occupancy profiling by high throughput sequencing</category>
|
||
<category>Methylation profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE272467 Spatial control of m6A deposition on enhancer and promoter RNAs by H3K27ac coordinated interaction between METTL3 and METTL14 [GLORI]</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272467</link>
|
||
<guid isPermaLink="false">GSE272467</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Xiang Huang ; Jinkai Wang ; Zhijun Ren ; Meijun Ye<br><i>Series Type</i> : Other ; Methylation profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Interaction between the m6A methyltransferase METTL3 and METTL14 is critical for METTL3 to deposit m6A on various types of RNAs. It is still intriguing whether there is spatial control of m6A deposition on different types of RNAs. Here, through genome-wide CRISPR/Cas9 screening based on a bimolecular fluorescence complementation (BIFC) reporter, we find the H3K27ac acetylase p300 and PAK2 inhibit the interaction between METTL3 and METTL14. We further find that p300-catalyzed acetylation of METTL3 specifically occurs on H3K27ac marked chromatin. METTL3 acetylation suppresses the binding of METTL3 on H3K27ac-marked chromatin by inhibiting its interaction with METTL14. Disruptive K-to-R mutations on the three METTL3 acetylation sites promote the m6A of chromatin-associated RNAs transcribed from p300 bound enhancers and promoters marked by H3K27ac and H3K4me1-3 other than those regions marked by H3K36me3 and H3K9me3, resulting in degradation of eRNAs and paRNAs and transcription inhibition of ferroptosis-inhibition related genes. In addition, PAK2 promotes METTL3 acetylation by phosphorylating METTL3. Inhibition of PAK2 promotes the ferroptosis induced by RSL3, ML162, as well as the chemotherapy drug CDDP in a manner that depends on the acetylation of METTL3. Our study reveals a spatial-selective way to specifically regulate the deposition of m6A on enhancer and promoter RNAs.</description>
|
||
<category>Other</category>
|
||
<category>Methylation profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE272466 Spatial control of m6A deposition on enhancer and promoter RNAs by H3K27ac coordinated interaction between METTL3 and METTL14 [CRISPR_screen]</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE272466</link>
|
||
<guid isPermaLink="false">GSE272466</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Xiang Huang ; Jinkai Wang ; Zhijun Ren ; Meijun Ye<br><i>Series Type</i> : Other<br><i>Organism</i> : Homo sapiens<p>Interaction between the m6A methyltransferase METTL3 and METTL14 is critical for METTL3 to deposit m6A on various types of RNAs. It is still intriguing whether there is spatial control of m6A deposition on different types of RNAs. Here, through genome-wide CRISPR/Cas9 screening based on a bimolecular fluorescence complementation (BIFC) reporter, we find the H3K27ac acetylase p300 and PAK2 inhibit the interaction between METTL3 and METTL14. We further find that p300-catalyzed acetylation of METTL3 specifically occurs on H3K27ac marked chromatin. METTL3 acetylation suppresses the binding of METTL3 on H3K27ac-marked chromatin by inhibiting its interaction with METTL14. Disruptive K-to-R mutations on the three METTL3 acetylation sites promote the m6A of chromatin-associated RNAs transcribed from p300 bound enhancers and promoters marked by H3K27ac and H3K4me1-3 other than those regions marked by H3K36me3 and H3K9me3, resulting in degradation of eRNAs and paRNAs and transcription inhibition of ferroptosis-inhibition related genes. In addition, PAK2 promotes METTL3 acetylation by phosphorylating METTL3. Inhibition of PAK2 promotes the ferroptosis induced by RSL3, ML162, as well as the chemotherapy drug CDDP in a manner that depends on the acetylation of METTL3. Our study reveals a spatial-selective way to specifically regulate the deposition of m6A on enhancer and promoter RNAs.</description>
|
||
<category>Other</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE269150 A hollow fiber membrane-based liver organoid-on-a-chip model for examining drug metabolism and transport</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269150</link>
|
||
<guid isPermaLink="false">GSE269150</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Adam Myszczyszyn ; Anna Münch ; Vivian Lehmann ; Theo Sinnige ; Frank G van Steenbeek ; Manon Bouwmeester ; Roos-Anne Samsom ; Marit Keuper-Navis ; Thomas K van der Made ; Sarah Braem ; Daniel Kogan ; Hossein Eslami Amirabadi ; Evita van de Steeg ; Rosalinde Masereeuw ; Bart Spee<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Liver-on-a-chip models predictive for both metabolism and transport of drug candidates in humans are lacking. Here, we have established an advanced, bioengineered and animal-free hepatocyte-like millifluidic system based on 3D hollow fiber membranes (HFMs), recombinant human laminin 332 and adult human stem cell-derived organoids. Organoid cells formed polarized and tight monolayers on HFMs, which displayed improved hepatocyte-like maturation over standard organoid cultures in Matrigel from matched donors. mRNA sequencing and immunofluorescence revealed that HFM cultures exhibited the expression of broad panel of phase I and II drug metabolizing enzymes, and of drug transporters. Functionally, in both static conditions and under flow circulation, HFM monolayers metabolized a cocktail of drugs that are targets for most important phase I and II enzymes. In addition, we were able to study disposition of those parental compounds and their metabolites in the basal circulation and apical compartment of the chip. Moreover, we demonstrated that our system can be used to study drug disposition in a modular setting with other PK/ADME-relevant organ systems. In conclusion, we have generated a proof-of-concept liver organoid-on-a-chip model for examining both metabolism and transport of drugs, which can be further developed towards prediction of PK/ADME profiles in humans.</description>
|
||
<category>Expression profiling by high throughput sequencing</category>
|
||
<category>Homo sapiens</category>
|
||
</item>
|
||
<item>
|
||
<title>GSE252487 Protein folding dependence on Selenoprotein M contributes to steady cartilage extracellular matrix repressing ferroptosis specifically access to PERK/ATF4/CHAC1 axis</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE252487</link>
|
||
<guid isPermaLink="false">GSE252487</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
||
<description><i>Contributors</i> : Yitong Zhao ; Ying Zheng ; Han Li ; Ru Wang<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Homo sapiens<p>Oateoarthritis (OA) commonly attends persistent inflammatory injury, extensive cartilage structural destruction and severe extracellular matrix (ECM) degradation. This study provides an overview of decreasing endoplasmic reticulum (ER)-resident selenoprotein M (SELM) probed into OA cartilage. Overexpression of SELM in chondrocytes positively promoted the synthesis of ECM. RNA-Seq results represented the mobilization of genes touched on various parts of degenerative diseases, inflammation and ferroptosis after SELM knockdown, which also negatively regulated cellular response to misfolded proteins and led to the activation of ER stress mediated by the PERK/P-EIF2A/ATF4 pathway in chondrocytes. Protein docking results captured that SELM was overwhelmingly likely to be involved in protein disulfide bond formation and modification processes by interacting with PDI, GRP94, CNX and CRT, resting on its thioredoxin domain. Decreased SELM also deepened GSH/GSSG homeostasis imbalance through the ATF4/CHAC1 axis and sparking ferroptosis. In vitro supplementation of SELM was buffering the effects of IL-1β on tattered cartilage explants. Furthermore, SELM also powered up the maintenance of favorable proliferative and homeostatic phenotypes among to an inhibitory effect on the hypertrophic phenotype in chondrocytes. These results make conclusive proof to unravel the involvement of SELM in ER stress induced cartilage damage and depict the distinctive function of SELM in protein folding, which renews directions for molecular therapeutic of degenerative diseases.</description>
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<category>Expression profiling by high throughput sequencing</category>
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<category>Homo sapiens</category>
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</item>
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<item>
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<title>GSE237964 The effect of pab2 deletion or clr4-1 mutation on gene expression in the fission yeast Schizosaccharomyces japonicus</title>
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE237964</link>
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<guid isPermaLink="false">GSE237964</guid>
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<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Ziyue LIU ; Tomoyasu SUGIYAMA<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Schizosaccharomyces japonicus<p>Pab2/PABPN1 is a nuclear poly(A)-binding protein, but its function is not fully understood yet. To investigate the Pab2 role in shaping transcriptome, we delete the pab2 gene in S. japonicus and characterize it. We found that meiosis-related genes are increased in pab2∆. Surprisingly, we observed the increases in transcripts derived from constitutive heterochromatin. Moreover, the upregulated and downregulated genes in pab2∆ and clr4 (the ortholog of the histone H3 Lys9 methyltransferase SUV39) mutant cells were significantly overlapped. Besides, constitutive heterochromatin is adversely affected in pab2∆. Our analyses demonstrate that Pab2 is required for the assembly of constitutive heterochromatin, and this finding provides a new insight into the Pab2 function(s).</description>
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<category>Expression profiling by high throughput sequencing</category>
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||
<category>Schizosaccharomyces japonicus</category>
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</item>
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<item>
|
||
<title>GSE226660 Hi-C of motor neurons under simulated microgravity (SMG) and normal gravity (NG)</title>
|
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<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE226660</link>
|
||
<guid isPermaLink="false">GSE226660</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
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<description><i>Contributors</i> : Danxia Huang ; Fei Yang<br><i>Series Type</i> : Other<br><i>Organism</i> : Homo sapiens<p>We differentiated motor neuron progenitor cells through small molecule combination and put them under microgravity and normal gravity respectively, and then performed gene expression profiling analysis using data obtained from RNA-seq of cells from 2 different group.</description>
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||
<category>Other</category>
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||
<category>Homo sapiens</category>
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</item>
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<item>
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||
<title>GSE168334 Single-cell RNA sequencing of inguinal and gonadal adipose stromal vascular fractions from wild-type C57BL/6J mice</title>
|
||
<link>http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE168334</link>
|
||
<guid isPermaLink="false">GSE168334</guid>
|
||
<pubDate>Wed, 05 Mar 2025 00:00:00 -0400</pubDate>
|
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<description><i>Contributor</i> : Hui Xie<br><i>Series Type</i> : Expression profiling by high throughput sequencing<br><i>Organism</i> : Mus musculus<p>Endothelial cells (ECs) have been reported to be a source of adipose tissue-derived stromal cells (ADSCs), and ADSCs expressing endothelial markers have been suggested to originate from ECs. To further investigate the lineage relationship between ECs and ADSCs in postnatal mice, we performed single-cell RNA sequencing (scRNA-seq) on ECs and ADSCs isolated from inguinal and gonadal white adipose tissues (IWATs and GWATs) of 12-week-old wild-type C57BL/6J mice, and analyzed the expression of endothelial markers in ADSCs.</description>
|
||
<category>Expression profiling by high throughput sequencing</category>
|
||
<category>Mus musculus</category>
|
||
</item>
|
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</channel>
|
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</rss>
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