GEO 数据集

主题由标题与摘要自动归类；样本量为数据集标注之和，SuperSeries 可能与其 SubSeries 重复计算。

• Acute Degradation of Pumilio Proteins Reveals a Biphasic Posttranscriptional Regulatory Hierarchy in Embryonic Stem Cell Fate Decision [iCLIP]
  GSE310693Mus musculus8 个样本2026-10-30

  Post-transcriptional regulation is critical for mammalian embryogenesis yet has been underexplored. We previously showed that RNA-binding Pumilio proteins (Pum1/2) are essential for early mouse embryogenesis and embryonic stem cell (ESC) functions. Here, using acute protein degradation systems combined with time-resolved RNA-seq and eCLIP, we delineate a two-phase regulatory hierarchy modulated by Pum1/2 in mouse ESCs. The first phase, occurring within 10 hours of Pum1/2 depletion, is predominantly the stabilization of over 100 Pum1/2-target mRNAs, while the second phase, occurring in subsequent 66 hours, propagates to over 1,000 mRNAs mostly through indirect regulatory effects. Functionally, Pum1/2 depletion delays transition from naïve to formative pluripotency, impairs neuroectoderm differentiation, and enhances germline specification. Mechanistically, Pum1/2 directly repress mRNAs encoding PRC2 subunits, including Suz12, thereby constraining H3K27me3 deposition at neuroectodermal gene loci. These findings establish Pum1/2 as biphasic post-transcriptional regulators of pluripotency and lineage balance and link RNA stability control to chromatin-mediated silencing.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health [Ribo-seq]
  GSE308616Mus musculus4 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives cardiometabolic disease. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage – characteristic of mitochondrial and lipogenic proteins.Together, our findings uncover a conserved translational control mechanism that regulates energy state in cellular metabolism.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health
  GSE308532Mus musculus9 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives conditions like cardiometabolic disease and obesity. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage - characteristic of mitochondrial and lipogenic proteins. Human genetic analyses and drug-target Mendelian Randomisation support a role for BUD23 in cardiometabolic traits and diseases. Together, our findings uncover a conserved translational control mechanism that regulates energy metabolism and offers a potential therapeutic target.
• HOXA9 Couples Transcriptional Control with Higher-Order Chromatin Architecture in Acute Myeloid Leukemia [HiC]
  GSE306376Homo sapiens6 个样本2026-10-30

  The three-dimensional (3D) genome is organized by architectural proteins such as CTCF and cohesin, while transcription factors (TFs) typically regulate enhancer–promoter (E–P) and enhancer-enhancer (E-E) communications without major structural effects. How these layers intersect remains unclear. Here, we reveal that the homeobox TF HOXA9—overexpressed in ~50% of acute myeloid leukemia (AML)—exerts a non-canonical architectural role. HOXA9 depletion in AML cells disrupts topologically associating domain (TAD) boundaries, dissolves chromatin loops, and perturbs cell-specific gene programs. We identify a distinct class of long-range “hybrid” loops (>250 kb) co-anchored by HOXA9 and convergent CTCF, frequently linked to TAD boundaries. Integrative analysis defines a 3D genome informed HOXA9 network and identifies NHLRC2 as a direct downstream target essential for leukemogenesis. Our findings establish HOXA9 as a dual-function TF that couples transcriptional control with higher-order genome architecture, offering a new mechanism for its pervasive activation across molecularly diverse AML subtypes.

  扰动筛选
• Multi-lineage evolution of drug resistance via a keratin 17+ aberrant basaloid drug tolerant persister population in EGFR-mutant NSCLC
  GSE303284Homo sapiens6 个样本2026-10-30

  We have an incomplete understanding of how EGFR-mutant drug tolerant persister cells (DTPCs) adapt to tolerate EGFR signaling blockade and whether these different mechanisms of resistance are present at baseline or emerge from a common DTPC population. In this study, we leveraged single cell RNA sequencing to comprehensively characterize phenotypes potentiating EGFR-mutant DTPCs and minimal residual disease states in part by sampling in vitro model systems. Using this and other single cell RNA sequencing data, we uncovered that a recurrent, novel KRT17+/KRT5- DTPC population harboring basaloid features and decreased alveolar lineage fidelity could give rise to diverse, multilineage mechanisms of targeted therapy resistance.

  单细胞
• HOXA9 Couples Transcriptional Control with Higher-Order Chromatin Architecture in Acute Myeloid Leukemia [RNA-seq]
  GSE301086Homo sapiens8 个样本2026-10-30

  The three-dimensional (3D) genome is organized by architectural proteins such as CTCF and cohesin, while transcription factors (TFs) typically regulate enhancer–promoter (E–P) and enhancer-enhancer (E-E) communications without major structural effects. How these layers intersect remains unclear. Here, we reveal that the homeobox TF HOXA9—overexpressed in ~50% of acute myeloid leukemia (AML)—exerts a non-canonical architectural role. HOXA9 depletion in AML cells disrupts topologically associating domain (TAD) boundaries, dissolves chromatin loops, and perturbs cell-specific gene programs. We identify a distinct class of long-range “hybrid” loops (>250 kb) co-anchored by HOXA9 and convergent CTCF, frequently linked to TAD boundaries. Integrative analysis defines a 3D genome informed HOXA9 network and identifies NHLRC2 as a direct downstream target essential for leukemogenesis. Our findings establish HOXA9 as a dual-function TF that couples transcriptional control with higher-order genome architecture, offering a new mechanism for its pervasive activation across molecularly diverse AML subtypes.

  扰动筛选
• Transcriptomic Changes of C.elegans in Subaqueous Acoustic Levitation Microgravity Device Artificial (Microgravity Environment).
  GSE301015Caenorhabditis elegans6 个样本2026-10-30

  To investigate the effects of a microgravity environment generated by the Subaqueous Acoustic Levitation Microgravity Device (SALMD) on biological systems, Caenorhabditis elegans were utilized as a model organism. A total of 8,000 C. elegans were cultured under standard conditions as the control group, while another 8,000 were cultured in microgravity environment via SALMD for 24 hours as the experimental group. Following exposure, the organisms were sacrificed for RNA extraction, and transcriptomic analysis was performed using bulk RNA sequencing.
• Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration [scATAC-seq]
  GSE297937Mus musculus2 个样本2026-10-30

  T cell development progresses through discrete stages that require precise control of gene activation and gene repression. Gene silencing is primarily mediated through epigenetic modifications, mediated by the interaction of transcription factors with repressor complexes containing chromatin-remodeling enzymes. Found within many such complexes, the corepressors NCOR1 and NCOR2 recruit histone deacetylases to suppress transcription of target genes. Using Cd4-cre mice, we identified multiple roles for NCOR1 and NCOR2 throughout thymocyte development. Here, we employed scATAC-seq to examine whether the RNA- and protein-level differences observed in these mice correlate with changes in chromatin accessibility.

  单细胞
• Heightened DOT1L-AF10 enriches H3K79me3 to promote pro-atherogenic inflammatory endothelial phenotype through NF-κB p65
  GSE295366Homo sapiens3 个样本2026-10-30

  DOT1L-catalyzed H3K79 methylation is a hallmark of actively transcribed genes and has been extensively studied in developmental and disease contexts. While DOT1L inhibition has emerged as a promising therapeutic strategy in cancer, its role in pro-atherogenic endothelial inflammation remains unclear. To investigate this, we utilized an in vivo partial carotid artery ligation model and observed increased DOT1L expression and H3K79me3 level. Consistently, in vitro studies employing a 3D-printed human coronary artery model and TNF-α stimulation corroborated these results, showing elevated DOT1L expression and H3K79me3 deposition, while levels of H3K79me and me2 remained unchanged. Further analyses identified key DotCom complex components, AF10 and AF9 (upregulated) and AF17 (downregulated), as contributors to the enhanced H3K79me3 landscape. CUT&RUN sequencing showed prominent H3K79me3 enrichment at the RELA (NF-κB p65) promoter, corresponding with increased NF-κB p65 expression and activation. Notably, inhibition/knockdown of the methyltransferase DOT1L or overexpression of the demethylase FBXL10 significantly reduced H3K79me3 levels, thereby suppressing NF-κB p65 expression and attenuating endothelial inflammation, independent of canonical NF-κB p65 activation. These findings establish DOT1L-mediated H3K79me3 as a crucial epigenetic regulator of endothelial inflammation, highlighting a potential therapeutic avenue for mitigating NF-κB p65-driven pro-atherogenic endothelial dysfunction.
• AR-V7 condensates drive androgen-independent transcription in castration resistant prostate cancer
  GSE292445Homo sapiens6 个样本2026-10-30

  Biomolecular condensates organize cellular environments and regulate key processes like transcription. We previously showed that full-length androgen receptor (AR-FL), a major oncogenic driver in prostate cancer (PCa), forms nuclear condensates upon androgen stimulation in androgen-sensitive PCa cells. Disrupting these condensates impairs AR-FL transcriptional activity, highlighting their importance. However, resistance to androgen deprivation therapy often leads to castration-resistant prostate cancer (CRPC), driven by constitutively active splice variants like AR variant 7 (AR-V7). The mechanisms underlying AR-V7’s role in CRPC remain unclear. We characterized AR-V7’s condensate-forming ability and compared its phase behavior with AR- FL across PCa models and in vitro. Our findings indicate that cellular context influences AR-V7’s condensate formation. Unlike AR-FL, AR-V7 spontaneously forms condensates without androgen stimulation and functions independently of AR-FL in CRPC. However, AR-V7 requires a higher concentration to form condensates in cells and in vitro. We reveal that AR-V7 drives transcription through condensate-dependent and independent mechanisms. Using an AR-V7 mutant incapable of forming condensates but retaining nuclear localization and DNA binding, we show the condensate-dependent regime activates part of the oncogenic KRAS pathway in CRPC. Genes under this regime harbored more AR-binding sites and exhibited boosted expression in response to AR-V7. These findings uncover AR-V7 condensates’ role in oncogenic transcription and CRPC progression.
• Lymphatic endothelium-restricted synthetic circuit therapy potentiates repair and chemoimmunotherapy response in a surgical lymphedema model
  GSE285323Mus musculus9 个样本2026-10-30

  Lymphedema is a frequent and difficult-to-treat surgical complication of various cancers involving lymph node dissection. Lymphangiogenic factor therapy is not clinically applied due to its pro-tumor effects. Here, our pharmacodynamic analysis and lymphovenous anastomosis intervention show that lymphedema is associated with reduced antitumor immunity in breast cancer patients. AAV delivery of lymphangiogenic factors mediated by Prox1, a LEC promoter, promotes tumor progression because of aberrant Prox1 activities in tumor cells. Therefore, we develop a LEC-specific synthetic circuit, LNCSMD, by adding staufen1-mediated mRNA decay (SMD) elements corresponding to high-throughput-identified tumor-specific lncRNAs. LNCSMD treatment abolishes unwanted outputs in tumor cells, induces lymphatic vessel repair and potentiates chemoimmunotherapy in vivo. We uncover that SMD can be harnessed as off-the-shelf synthetic circuit treatment for lymphedema.
• Species-Dependent WNT/ß-Catenin Signaling Orchestrates Epiblast Morphogenesis during Early Implantation [Cut & Run]
  GSE273593Homo sapiens4 个样本2026-10-30

  The precise orchestration of epiblast tissue remodeling during implantation is critical for mammalian embryonic development and the regulatory link between cellular signaling and epiblast tissue morphogenesis remains unexplored. We present a fully defined, 3D epiblast-like model derived from human pluripotent stem cells (hPSCs). Functional studies of these in vitro models, alongside in vivo investigations in human and mouse embryos, reveal the pivotal role of canonical WNT signaling in mammalian epiblast morphogenesis. In humans, WNT/β-catenin signaling is crucial for epithelization, rosette formation, and cavitation of epiblast tissue. In mice, inhibition of canonical WNT signaling supports these events. Dual CUT&RUN and RNA sequencing, complemented by multi-study comparative transcriptome profiling, identify a TCF/LEF-mediated mechanism linking WNT signaling to lipid metabolism in human epiblast morphogenesis. This study highlights divergent roles of WNT-mediated mechanisms in early mouse and human development, as well as potential causes of human embryo lethality at implantation.
• Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration
  GSE246149Mus musculus3 个样本2026-10-30

  T cell development proceeds via discrete stages that require both gene induction and gene repression. Transcription factors direct gene repression by associating with corepressor complexes containing chromatin-remodeling enzymes; the corepressors NCOR1 and NCOR2 recruit histone deacetylases to these complexes to silence transcription of target genes. Earlier work identified the importance of NCOR1 in promoting the survival of positively-selected thymocytes. Here, we used flow cytometry and single cell RNA sequencing to identify a broader role for NCOR1 and NCOR2 in regulating thymocyte development. Using Cd4-cre mice, we found that conditional deletion of NCOR2 had no effect on thymocyte development, whereas conditional deletion of NCOR1 had a modest effect. In contrast, Cd4-cre x Ncor1f/f x Ncor2f/f mice exhibited a significant block in thymocyte development at the DP to SP transition. Combined NCOR1/2 deletion resulted in increased signaling through the T cell receptor, ultimately resulting in elevated BIM expression and increased negative selection. The NF-κB, NUR77, and MAPK signaling pathways were also upregulated in the absence of NCOR1/2, contributing to altered CD4/CD8 lineage commitment, TCR rearrangement, and thymocyte emigration. Taken together, our data identify multiple critical roles for NCOR1/2 throughout thymocyte development.

  单细胞
• Identification of 2’-O-methylation sites on mRNA and pre-mRNA
  GSE188194Homo sapiens6 个样本2026-10-30

  There have been reports suggesting that there may be thousands of Nm-modified mRNA or pre-mRNA transcripts in mammalian cells, there have been no studies that validate the proposed sites or determine the molecular mechanism responsible for their placement. In this study, we have refined a method for transcriptome-wide mapping of Nm sites and identified numerous high-confidence sites in mature mRNA
• Metabolic trapping of arachidonic acid by Treg cells shapes CD8+ T cell anti-tumor immunity
  GSE352441Mus musculus7 个样本2026-10-29

  Regulatory T (Treg) cells rely on lipid metabolism to thrive in the lipid-rich tumor microenvironment (TME), but whether this metabolism shapes the extracellular metabolite landscape that acts on effector T cells remains unknown. Here, we identify epoxide hydrolase 1 (Ephx1), highly expressed in tumor-infiltrating Treg cells, as a cell-intrinsic determinant of arachidonic acid (AA) availability in the TME. Treg-specific deletion of Ephx1 induced compensatory, ACSL4-dependent incorporation of exogenous AA, converting Treg cells into a metabolic trap for tumor-derived AA and lowering its extracellular abundance. The resulting AA scarcity restored the mitochondrial fitness of CD8⁺ T cells, rewired their metabolism away from fatty acid oxidation toward more efficient energy generation, and skewed exhaustion trajectories toward effector-like intermediate states while preserving the stem-like progenitor pool, collectively restraining tumor progression. In patients with hepatocellular carcinoma, TME AA levels tracked with tumor burden and inversely with the mitochondrial fitness of infiltrating CD8⁺ T cells. Accordingly, intratumoral delivery of the AA-release inhibitor Methyl Arachidonyl Fluorophosphonate (MAFP) reinvigorated CD8⁺ T cell immunity and acted synergistically with anti-PD-1 therapy. Targeting Treg cell lipid metabolism thus offers a route to reprogram the TME metabolome and potentiate cancer immunotherapy.
• BAP1 safeguards double-strand DNA break repair by limiting DNA end resection [ChIP-Seq]
  GSE352106Homo sapiens5 个样本2026-10-29

  The tumor suppressor BAP1 is frequently mutated in uveal melanoma and has been linked to homologous recombination (HR), yet how it influences DNA double-strand break (DSB) repair pathway choice remains unclear. Here, we identify BAP1 as a critical regulator that restricts DNA end resection to preserve non-homologous end-joining (NHEJ) capacity. Loss of BAP1 leads to aberrant accumulation of H2AK119 ubiquitination at DSBs, driving unscheduled resection in G1-phase cells and impairing recruitment of the anti-resection factor 53BP1. Co-depletion of the resection initiator CtIP restores NHEJ efficiency in BAP1-depleted cells, and pharmacological suppression of H2AK119 ubiquitination reverses these defects, placing unscheduled resection causally upstream of the end-joining failure. RNA sequencing and genome-wide H2AK119ub profiling show that neither the expression of NHEJ and HR genes nor the H2AK119ub landscape at their promoters is appreciably altered by BAP1 loss, supporting a role of altered H2AK119ub at the DSBs. These findings indicate that BAP1 safeguards DSB repair fidelity by preventing hyper-resection, thereby maintaining NHEJ competence. Consistent with this role, BAP1-depleted cells accumulate micronuclei, and BAP1 loss is associated with genomic instability in human uveal melanoma. Together, our results uncover a mechanism by which chromatin regulation constrains resection to coordinate repair pathway utilization.
• SH2 Domain Protein E sustains perivascular fibroblasts to maintain arterial stability
  GSE352057Danio rerio8 个样本2026-10-29

  Developing arteries must withstand pulsatile blood flow while remaining sufficiently flexible to accommodate changing hemodynamic demands. Endothelial interactions with perivascular cells and extracellular matrix are essential for this balance, but the signaling mechanisms that coordinate them remain incompletely understood. We previously showed that SH2 domain protein E (She), an endothelial adaptor protein implicated in ABL signaling, limits the size of the dorsal aorta (DA) in zebrafish embryos. Here, we investigated why zebrafish she mutants subsequently develop DA collapse and circulatory failure at 4–5 days post-fertilization. Before circulatory failure, the mutant DA retained an approximately circular cross-section and showed no detectable changes in the endothelial cell geometry, but exhibited increased distensibility during the cardiac cycle. Mutants had fewer perivascular stromal cells between the DA and posterior cardinal vein, smaller perivascular col1a1 and col5a1 expression domains, and reduced col1a1 transcript level. Single-cell RNA sequencing independently identified a reduced relative abundance of perivascular fibroblast subpopulation. In contrast, DA-associated mural cell numbers, laminin immunoreactivity, and local col4a1 transcript levels were not detectably altered. Ablation of pdgfrb-positive cells largely prevented DA narrowing and circulatory failure, while the nitric oxide donor sodium nitroprusside provided partial rescue. These findings support a contribution of mural cell-dependent vascular tone to collapse of the mechanically vulnerable DA. Mutants also exhibited cardiac chamber enlargement, increased atrial and bulbus arteriosus deformation, atrioventricular regurgitation, and increased Elastin B accumulation in the enlarged bulbus arteriosus. However, endocardial-specific She expression failed to rescue circulatory failure, supporting its requirement in vascular endothelium. Together, these findings link She function to perivascular fibroblast abundance, fibrillar collagen-gene expression, and arterial stability. They support a model in which impaired perivascular support renders the developing DA susceptible to mural cell-associated collapse, extending the role of She from early vessel-size regulation to maintenance of vascular function.

  单细胞
• Transcriptional response of primary human pancreatic cancer-associated fibroblasts to IFN-γ and lipopolysaccharide stimulation
  GSE348821Homo sapiens9 个样本2026-10-29

  Single-cell analysis of a pan-cancer tumor microenvironment atlas identified transcriptionally distinct inflammatory cancer-associated fibroblast (iCAF) subpopulations, including an ISG15+ iCAF population predicted to arise downstream of interferon-γ signaling from CD8+/GZMB+ T cells, and a CXCL8+ iCAF population. To test these predictions experimentally, primary cancer-associated fibroblasts (CAFs) were isolated from a fresh human pancreatic ductal adenocarcinoma (PDAC) surgical specimen, expanded in culture, and treated for 24 hours with control media, recombinant human interferon-γ, or lipopolysaccharide (LPS). Bulk RNA-sequencing of the resulting nine libraries was used to compare the induced transcriptional programs against gene signatures derived from the ISG15+ iCAF and CXCL8+ iCAF subpopulations of the atlas. Results are reported in the associated publication.

  单细胞细胞图谱
• Prenatal maternal cold stress exposure drives sex-specific neurodevelopmental disruptions in the fetal hypothalamus
  GSE328919Mus musculus3 个样本2026-10-29

  The prevalence of neurodevelopmental disorders (NDDs) is increasing, with growing evidence implicating the intrauterine environment as a critical regulator of fetal brain development. Gestational perturbations such as maternal stress can increase NDD risk; however, the mechanism(s) by which prenatal maternal stress reshape fetal neurodevelopment remain unclear. Accordingly, the objective of my project was to characterize how maternal cold stress exposure during pregnancy disrupts neural stem and progenitor cell (NSPC) developmental programs in the fetus and the impact this has on neurodevelopment in the hypothalamus. Pregnant mice were exposed to 4°C for 30 minutes daily from embryonic day 11.5 (E11.5) to E15.5—a critical period of neurodevelopment in the hypothalamus. To assess how maternal cold stress impacts neural stem cell (NSC) behaviours, we employed the neurosphere assay, quantifying the number and size of primary and secondary neurospheres as a measure of NSC proliferation and self-renewal, respectively. Our findings revealed no change in NSC proliferation or self-renewal when comparing control and maternal cold stress male and female neurospheres. However, differentiation of dissociated NSCs revealed that neurons from both sexes had longer axons following maternal cold stress exposure. Interestingly, only male-derived cultures exhibited a significant increase in the number TUJ1+ neurons in response to maternal cold stress exposure, whereas only female-derived maternal cold stress cultures showed enhanced dendritic arborization. To explore the molecular basis of these changes, we performed single-cell RNA sequencing on E15.5 fetal hypothalamic NSPCs. Analysis of differentially expressed genes uncovered basal sex differences between the transcriptional signatures of control male and female Cycling NSPCs and suggested that maternal cold stress shifts female Cycling NSPCs toward a more male-like transcriptional profile. Gene ontology analysis revealed that maternal cold stress upregulates pathways linked to neuronal growth, development, and GABAergic neuron differentiation, but only in females. Importantly, ligand-receptor analysis suggested that maternal cold stress exposure disrupts neurodevelopmental programs through altered cell-cell signalling within Cycling NSPCs predominantly in females. These findings demonstrate that prenatal maternal cold stress exposure drives sex-specific effects on fetal neurodevelopment and uncover distinct cellular pathways that may contribute to sex differences seen in the presentation and risk of many NDDs.

  单细胞扰动筛选
• AP-1 Family Member Transcription Factors Play a Critical Role in Human Beta Cell Replication and Differentiation [scATAC-seq]
  GSE326466Homo sapiens3 个样本2026-10-29

  Insulinomas are a rare and benign type of pancreatic neuroendocrine tumor. They consist of pancreatic beta cells that are able to replicate as opposed to their human islet counterparts. They are also able to secrete insulin. Although we know epigenetics is a critical factor, it is unclear which exact pathways play a role in the control of replication and differentiation. Here we performed snATAC-seq to gain further insight into the open accessible chromatin regions in various insulinoma cell types.

  单细胞
• AP-1 Family Member Transcription Factors Play a Critical Role in Human Beta Cell Replication and Differentiation [Multiome]
  GSE326458Homo sapiens2 个样本2026-10-29

  Insulinomas are a rare and benign type of pancreatic neuroendocrine tumor. They consist of pancreatic beta cells that are able to replicate as opposed to their human islet counterparts. They are also able to secrete insulin. Although we know epigenetics is a critical factor, it is unclear which exact pathways play a role in the control of replication and differentiation. Here we performed multiome assay to delineate open accessible chromatin regions and single cell transcriptomic profiles in various insulinoma cell types.

  单细胞多组学
• AP-1 Family Member Transcription Factors Play a Critical Role in Human Beta Cell Replication and Differentiation [snRNA-seq]
  GSE326455Homo sapiens2 个样本2026-10-29

  Insulinomas are a rare and benign type of pancreatic neuroendocrine tumor. They consist of pancreatic beta cells that are able to replicate as opposed to their human islet counterparts. They are also able to secrete insulin. Although we know epigenetics is a critical factor, it is unclear which exact pathways play a role in the control of replication and differentiation in insulinomas. Here we performed snRNAseq to gain further insight into the transcriptomic profiles of various insulinoma cell types.

  单细胞
• AP-1 Family Member Transcription Factors Play a Critical Role in Human Beta Cell Replication and Differentiation [ChIP-seq]
  GSE326450Homo sapiens7 个样本2026-10-29

  Insulinomas are a rare and benign type of pancreatic neuroendocrine tumor. They consist of pancreatic beta cells that are able to replicate as opposed to their human islet counterparts. They are also able to secrete insulin. Although we know epigenetics is a critical factor, it is unclear which exact pathways play a role in the control of replication and differentiation in insulinomas. Here we performed bulk RNA-seq to gain further insight into the transriptomic profiles of insulinomas and FACS-sorted beta cells.
• AP-1 Family Member Transcription Factors Play a Critical Role in Human Beta Cell Replication and Differentiation [ATAC-seq]
  GSE326447Homo sapiens7 个样本2026-10-29

  Insulinomas are a rare and benign type of pancreatic neuroendocrine tumor. They consist of pancreatic beta cells that are able to replicate as opposed to their human islet counterparts. They are also able to secrete insulin. Although we know epigenetics is a critical factor, it is unclear which exact pathways play a role in the control of replication and differentiation in insulinomas. Here we performed bulk ATAC-seq to gain further insight into the open accessible chromatin regions in insulinomas and FACS-sorted beta cells.
• Spatially resolved heterogeneity of lymphatic vasculature in the adult lung
  GSE325297Mus musculus2 个样本2026-10-29

  Background. Lung lymphatic drainage of interstitial fluid is essential for preventing pulmonary edema, a condition characterized by the accumulation of extravascular fluid that impedes respiratory gas exchange and can be fatal. Beyond fluid regulation, lung lymphatics also serve as conduits for immune cell trafficking, supporting both surveillance and mounting of host immune responses during lung infection. Despite their essential roles, the cellular and functional heterogeneity of lung lymphatic endothelial cells (LECs) remains poorly defined. Methods. Leveraging single nucleus sequencing technology, we investigated LEC heterogeneity in the homeostatic adult mouse lung. Results. We identified Stabilin-2 (Stab2), a Class H scavenger receptor, as a unique marker of a distinct subset of LECs in lymphatic vessels adjacent to pulmonary veins and in alveolar regions. A separate distinct subset of LECs is defined by expression of Polycystic Kidney and Hepatic Disease 1-Like-1 (Pkhd1l1), a component of stereocilia, and these lymphatic vessels are localized to the bronchovascular bundle. Conclusions. Our findings suggest that lung LECs are not a uniform population but instead compromise molecularly distinct and spatially organized lymphatic vessels, possibly with specialized functions. These results lay the groundwork for further studies geared towards understanding the roles of cellular origin in lung LEC heterogeneity, whether lymphatics in other organs have analogous spatial organization, and whether these disparate cells and vessels have functional differences in fluid homeostasis and immune regulation during pulmonary disease pathogenesis.

  单细胞空间转录组
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons [scRNA-Seq]
  GSE317781Mus musculus2 个样本2026-10-29

  The transcriptional and epigenetic mechanisms that govern neuronal subtype differentiation and diversification remain poorly defined, with auditory neurons among the least understood. Here, we investigate the role of the proneural factor NEUROD1 using a delayed, self terminating conditional knockout (Neurod1ST) mouse model that bypasses the early neuronal loss observed in germline mutants. By integrating NEUROD1 chromatin binding and histone profiling at E11.5 with transcriptomic analyses at E11.5, E14.5, and E18.5, we show that NEUROD1 is essential for coordinating the timing of neuronal differentiation. Neurod1 deletion prolongs progenitor-like states while prematurely accelerating differentiation and axonogenesis programs, reflecting the collapse of NEUROD1-dependent transcriptional networks and recruitment of compensatory pathways. NEUROD1 preferentially binds enhancers of neuronal differentiation genes and promotes their transition to active chromatin states, consistent with a pioneer factor function. Loss of Neurod1 disrupts these epigenomic transitions, alters neuronal migration and innervation trajectories, and ultimately leads to neuronal instability and apoptosis. During spiral ganglion neuron diversification, Neurod1ST neurons prematurely activate maturation markers and fail to generate Type Ic, instead adopting a Type Ib-like identity. These findings establish NEUROD1 as a central regulator that synchronizes differentiation, stabilizes neuronal identity, and shapes auditory neuron subtype diversity in the developing inner ear

  单细胞
• A CRISPR-Based Humanized Model Reveals Cooperative Role of STAG2 Loss in Familial GATA2-Deficient MDS Progression
  GSE317264Homo sapiens6 个样本2026-10-29

  Myelodysplastic syndrome is a heterogeneous myeloid malignancy driven by hematopoietic stem cell dysfunction, leading to ineffective hematopoiesis and cytopenias. Familial GATA2 deficiency is the most common cause of Myelodysplastic syndrome in adolescents, with progression often accelerated by co-occurring mutations, notably STAG2 loss-of-function. Using CRISPR/Cas9-mediated genome engineering in primary human fetal liver-derived hematopoietic stem cells and xenotransplantation in mice, we modeled GATA2-deficient Myelodysplastic syndrome with acquired STAG2 loss to investigate disease initiation and progression. While GATA2 deficiency alone had minimal short-term impact in our model, combined GATA2 and STAG2 loss increased hematopoietic stem cell maintenance and self-renewal, induced a myeloid-lineage bias, and expanded primitive progenitors. Single-cell transcriptional profiling revealed upregulation of stemness genes and inflammatory pathways, alongside downregulation of MYC targets. This humanized model faithfully recapitulates high-risk GATA2-deficient Myelodysplastic syndrome, providing mechanistic insight into how cooperative mutations drive stem cell expansion, inflammatory signaling, and myeloid skewing.

  单细胞
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons [snRNA-Seq]
  GSE315741Mus musculus2 个样本2026-10-29

  The transcriptional and epigenetic mechanisms that govern neuronal subtype differentiation and diversification remain poorly defined, with auditory neurons among the least understood. Here, we investigate the role of the proneural factor NEUROD1 using a delayed, self terminating conditional knockout (Neurod1ST) mouse model that bypasses the early neuronal loss observed in germline mutants. By integrating NEUROD1 chromatin binding and histone profiling at E11.5 with transcriptomic analyses at E11.5, E14.5, and E18.5, we show that NEUROD1 is essential for coordinating the timing of neuronal differentiation. Neurod1 deletion prolongs progenitor-like states while prematurely accelerating differentiation and axonogenesis programs, reflecting the collapse of NEUROD1-dependent transcriptional networks and recruitment of compensatory pathways. NEUROD1 preferentially binds enhancers of neuronal differentiation genes and promotes their transition to active chromatin states, consistent with a pioneer factor function. Loss of Neurod1 disrupts these epigenomic transitions, alters neuronal migration and innervation trajectories, and ultimately leads to neuronal instability and apoptosis. During spiral ganglion neuron diversification, Neurod1ST neurons prematurely activate maturation markers and fail to generate Type Ic, instead adopting a Type Ib-like identity. These findings establish NEUROD1 as a central regulator that synchronizes differentiation, stabilizes neuronal identity, and shapes auditory neuron subtype diversity in the developing inner ear

  单细胞
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons [scRNAseq_E115]
  GSE315597Mus musculus2 个样本2026-10-29

  The transcriptional and epigenetic mechanisms that govern neuronal subtype differentiation and diversification remain poorly defined, with auditory neurons among the least understood. Here, we investigate the role of the proneural factor NEUROD1 using a delayed, self terminating conditional knockout (Neurod1ST) mouse model that bypasses the early neuronal loss observed in germline mutants. By integrating NEUROD1 chromatin binding and histone profiling at E11.5 with transcriptomic analyses at E11.5, E14.5, and E18.5, we show that NEUROD1 is essential for coordinating the timing of neuronal differentiation. Neurod1 deletion prolongs progenitor-like states while prematurely accelerating differentiation and axonogenesis programs, reflecting the collapse of NEUROD1-dependent transcriptional networks and recruitment of compensatory pathways. NEUROD1 preferentially binds enhancers of neuronal differentiation genes and promotes their transition to active chromatin states, consistent with a pioneer factor function. Loss of Neurod1 disrupts these epigenomic transitions, alters neuronal migration and innervation trajectories, and ultimately leads to neuronal instability and apoptosis. During spiral ganglion neuron diversification, Neurod1ST neurons prematurely activate maturation markers and fail to generate Type Ic, instead adopting a Type Ib-like identity. These findings establish NEUROD1 as a central regulator that synchronizes differentiation, stabilizes neuronal identity, and shapes auditory neuron subtype diversity in the developing inner ear

  单细胞
• Non-canonical RNA binding of the MYBL2 transcription factor promotes melanoma (CLIP-seq)
  GSE284545Homo sapiens3 个样本2026-10-29

  Melanoma originates from melanocytes, and the process of melanocyte malignant transformation is affected by various factors, including non-mutational gene alterations. MYBL2 is a transcription factor primarily known for its role in regulating cell cycle progression. In this study, we characterized that MYBL2 gain or amplification occurs in one fifth of the melanoma patients, and the aberrantly upregulated MYBL2 promotes melanoma growth while representing a melanoma vulnerability. Notably, MYBL2 can also binds RNA, and its oncogenic effect is mediated through its RNA binding function. Crosslinking-immunoprecipitation followed by high-throughput sequencing revealed that MYBL2 primarily binds protein-coding genes and introns. Interestingly, MYBL2 does not affect the RNA metabolism of its direct targets. Instead, its RNA binding function influences its association with chromatin and thereby rewiring the transcription program favoring poor patient survival. Surprisingly, we observed that MYBL2 binds RNA exclusively in melanoma cells, but not in melanocytes. This phenomenon is primarily due to the altered RNA background developed following melanoma transformation, while alternations within MYBL2 itself also involved in a lesser extent. Therefore, our work identified a novel oncogenic function of MYBL2 through its RNA binding activity, extending our current understanding of MYBL2 and highlighting a critical mechanism in melanoma progression.