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。

• 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.
• Gene expression profile and TCR-sequencing at single-cell level of PBMCs responding to EBV after 6 days of in vitro incubation.
  GSE277638Homo sapiens24 个样本2026-10-30

  In this work, we were able to establish a protocol for PBMC infection and sequence, for the first time at a single-cell level, the transcriptome of all cells capable of responding to the Epstein-Barr virus in healthy individuals and in certain patients with Inborn Errors of Immunity. Cells were sorted prior to sequencing based on proliferation (dilution of Cell Trace Violet) or activation (expression of CD69 and/or CD25).

  单细胞
• Species-Dependent WNT/ß-Catenin Signaling Orchestrates Epiblast Morphogenesis during Early Implantation [RNA-Seq]
  GSE273623Homo sapiens15 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.
• 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.
• Exploration of microRNAs involved in cervical lymph node metastasis of oral squamous cell carcinoma
  GSE246620Homo sapiens12 个样本2026-10-30

  Exploring biomarkers involved in lymph node metastasis in oral cancer
• 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
• Trisomy 21 Perturbs Oligodendrocyte Developmental States and Oligo-Neuron Communication in Human Forebrain Assembloids
  GSE352389Homo sapiens12 个样本2026-10-29

  Intellectual disability is a hallmark of Down syndrome (DS), caused by the triplication of human chromosome 21. Abnormal neuronal connectivity and impaired myelination are consistently observed in DS, yet the underlying mechanisms remain poorly understood. Here, we used DS-derived isogenic induced pluripotent stem cell-derived forebrain assembloids (FAs) to investigate oligodendrocyte lineage cell (OLLC) development and neuron-glia interactions. Trisomic FAs exhibited an expansion of BCAS1+ pre-myelinating OLLCs, without a corresponding increase in myelin basic protein (MBP) expression. Transcriptomic analyses identified a euploid-enriched, trophic and maturation-supportive state (OLLC_2-TMS) and a trisomy-enriched state, characterized by enhanced neuronal interactions and restricted progression beyond the pre-myelinating stage (OLLC_3-NID). These transcriptional signatures were also present in OLLCs from early postnatal human cortex. Increased excitatory neuronal contacts with pre-myelinating OLLCs accompanied ultrastructural myelin abnormalities in trisomic assembloids. Our findings suggest that trisomy redirects OLLC development toward a pre-myelinating state, uncoupling oligodendrocyte differentiation from productive myelination.

  扰动筛选
• 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.
• RNA-seq of human meningioma samples
  GSE351918Homo sapiens59 个样本2026-10-29

  Meningiomas are frequently diagnosed tumors of intracranial location. In the WHO classification, tumor aggressiveness is assessed by assigning increasing grades, with WHO grade I tumors considered benign and WHO grade III tumors the most aggressive. In our study, we aimed to identify biological features associated with meningioma aggressiveness by profiling gene expression in FFPE tumor samples of different WHO grades (I, II, and III).
• Cancer-Associated Transcriptional Readthrough Reveals Distinct Stress- and Proliferation-Related Programs
  GSE349075Homo sapiens47 个样本2026-10-29

  Transcriptional readthrough generates downstream-of-gene (DoG) RNAs through transcription beyond canonical termination sites. Although DoGs have been implicated in cellular stress and cancer, their biological and clinical significance remains poorly understood. We analyzed DoG transcripts in 787 experimental and 3,066 public RNA-seq profiles encompassing colorectal, lung, pancreatic, stomach, and thyroid cancers. RNA-seq library design strongly influenced DoG detection, with rRNA-depleted and paired-end libraries providing greater sensitivity than poly(A)-selected and single-end approaches. DoG abundance and expression were increased in most cancer types, whereas DoG length was largely unchanged. Joint analysis of DoG and parental gene expression identified two distinct classes of cancer-associated readthrough. DoGs upregulated independently of parental genes, consistent with dysregulated transcription termination, included 31 transcripts recurrently increased across all five cancer types and were associated with stress-related functions. In contrast, DoGs co-upregulated with their parental genes were enriched for proliferation-related processes. In an experimental cohort of 95 lung cancer patients receiving PD-(L)1 immune checkpoint therapy, higher abundance and expression of recurrent DoG signatures were associated with shorter progression-free survival (HR 2.53–3.24). These findings reveal distinct biological components of cancer-associated transcriptional readthrough and identify recurrent DoG signatures as candidate prognostic biomarkers.
• 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
• Multi-omics analysis reveals an EXOSC10-lncRNA-dependent checkpoint in nucleolar proteostasis recovery
  GSE329077Homo sapiens12 个样本2026-10-29

  Proteotoxic stress induced by heat shock drives the formation of nucleolar aggresomes. However, the mechanisms governing their resolution during recovery remain poorly understood. Here, we combine temporal quantitative proteomics, transcriptomics and live imaging to define the dynamics of the detergent-insoluble fraction during heat shock and recovery. We find that nucleolar aggresome recovery follows a multiphasic lag–burst–resolution kinetic program that tightly couples the recruitment of protein quality-control factors and remobilization of ribosomal proteins. We identify stress-induced long non-coding RNA IGS16 as a critical regulator of this process. IGS16 accumulates in the nucleolus upon heat shock where it restrains chaperone engagement. Clearance of IGS16 by the nucleolar exonuclease EXOSC10 is required to initiate nucleolar remodeling and enable HSP70-dependent restoration of ribosomal protein mobility. Notably, IGS16 degradation occurs independently of HSP70 ATPase activity, indicating that RNA turnover precedes and licenses chaperone-mediated aggregate resolution. Together, our findings uncover an RNA-dependent regulatory checkpoint that coordinates RNA metabolism and protein quality control to regulate nucleolar proteostasis recovery. This work also reveals a previously unknown function for EXOSC10 in stress-induced condensate dynamics control potentially through long non-coding RNA degradation.

  多组学
• AP-1 Family Member Transcription Factors Play a Critical Role in Human Beta Cell Replication and Differentiation
  GSE327169Homo sapiens21 个样本2026-10-29

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• 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.
• 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
• 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.
• Non-canonical RNA binding of the MYBL2 transcription factor promotes melanoma (RNA-seq)
  GSE284544Homo sapiens12 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.
• Transcriptomic profiling of ECV304 cells under normoxic, hypoxic, and hypoxia-tolerant conditions
  GSE352293Homo sapiens9 个样本2026-10-28

  This study investigated transcriptomic changes in ECV304 cells under normoxic, hypoxic, and hypoxia-tolerant conditions. Cells were assigned to three groups, each with three biological replicates. The hypoxia group was exposed to 3% O2 for 24 h, whereas hypoxia tolerance was established by repeated hypoxia-reoxygenation cycles (cycle details to be confirmed). Total RNA was subjected to paired-end RNA sequencing on an Illumina NovaSeq 6000. The dataset supports comparisons of gene expression patterns associated with acute hypoxia and hypoxia tolerance.
• QUAIL-100 Induces Distinct, Multifunctional γδ T Cell Responses with Enhanced Durability Compared to Zoledronic Acid in Post-HSCT Pediatric Leukemia Patients
  GSE352026Homo sapiens21 个样本2026-10-28

  γδ T cells mediate potent anti-leukemic and anti-infective immunity following allogeneic hematopoietic stem cell transplantation (HSCT); however, standard Vγ9Vδ2 activation with zoledronic acid (ZOL) induces rapid terminal differentiation and functional exhaustion, limiting sustained therapeutic efficacy. Pathogen-driven γδ T cell responses, including those elicited by cytomegalovirus (CMV), exhibit greater functional diversity and durability, providing a conceptual framework for multimodal activation strategies. QUAIL-100, a quadruple-attenuated Listeria monocytogenes strain (Lm ΔactA/ΔinlB/ΔribC/ΔribF), was evaluated as a novel γδ T cell activator that engages combinatorial signals including phosphoantigens, pathogen-associated molecular patterns, and co-stimulatory pathways.
• Tau A152T risk variant drives distinct cell type transcriptional signatures in AD and PSP
  GSE350921Homo sapiens28 个样本2026-10-28

  The A152T point mutation is a rare genetic variant in the tau gene (MAPT) that is linked to risk of Alzheimer’s disease (AD) and frontotemporal dementia spectrum disorders, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). To uncover mechanisms through which the A152T variant contributes to risk of tauopathy, we performed single-nucleus RNA sequencing (snRNA-seq) on postmortem brain tissue collected from A152T carriers and pathology-matched non-carriers with either AD or PSP, along with age-matched controls. These efforts revealed that despite similar cell type composition across groups, A152T carriers exhibited distinct cell type-specific transcriptional changes in both AD and PSP. Differential expression analysis identified excitatory neurons, oligodendrocytes and astrocytes as the most affected cell populations in AD and PSP, and these same cell types showed the strongest A152T-specific changes. These findings identify transcriptional alterations that differentiate sporadic AD and sporadic PSP from AD-A152T and PSP-A152T, as well as shared molecular signatures unique to A152T carriers in both PSP and AD. Donor-level pseudobulk analyses showed broad directional support with the single-nucleus findings, although the proportion of donor-supported genes varied across cell type and comparison. Importantly, merging sporadic and A152T cases into a single disease group was found to mask transcriptional differences in several cell types in both AD and PSP, indicating divergence in transcriptional signature and highlighting the importance of screening for genetic risk variants like A152T in snRNA-seq data from human cohorts.

  单细胞
• Paired Transcriptomic Profiling Identifies Shared Liver Metas-tasis-Associated Molecular Features in Colorectal Cancer
  GSE347316Homo sapiens12 个样本2026-10-28

  Colorectal cancer liver metastasis (CCLM) is closely associated with poor patient prognosis, yet patient-specific molecular heterogeneity complicates the identification of recurrent molecular changes during metastasis. To address this, we performed RNA sequencing on paired primary tumors and liver metastases synchronously resected from six patients and analyzed gene expression changes using a paired design that accounted for interpatient variability. This analysis identified differentially expressed genes (DEGs) and metastasis-associated pathways through functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). The reproducibility of these changes was further assessed across multiple independent publicly available transcriptomic datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Selected candidate genes were additionally evaluated in a metastasis-selected colorectal cancer cell model, in which several genes showed expression changes consistent with the transcriptomic findings. Together, these results indicate that recurrent molecular changes accompany CCLM despite substantial interpatient heterogeneity and provide a strategy for identifying metastasis-associated molecular features and potential therapeutic targets

  细胞图谱
• Super-enhancer NR125945 drives prostate cancer malignancy via long-range chromatin interactions [RNA-Seq]
  GSE346320Homo sapiens12 个样本2026-10-28

  Genetic susceptibility plays an essential role in prostate cancer (PCa) risk, while the functional mechanisms underlying several classic risk loci remain largely uncharacterized. Here, we identified a PCa specific super-enhancer within 1q42.3 locus, termed NR125945-SE. Through comparative H3K27ac ChIP-seq analysis, we observed that NR125945-SE is highly active in PCa cells compared to normal controls. NR125945-SE contributes to PCa malignant progression. Mechanistically, integrative analysis combining RNA-seq and 4C-seq data revealed that NR125945-SE regulates the expression of CAPN2 and KRT19 through long-range chromatin interactions. Furthermore, we demonstrated that NR125945-SE activity is mediated by the cooperative binding of multiple transcription factors. In summary, our findings provide insights into a functional epigenetic element within a classic genetic risk locus, proposing a mechanism by which super-enhancer-mediated regulation promotes prostate cancer progression.
• Super-enhancer NR125945 drives prostate cancer malignancy via long-range chromatin interactions [CUT&Tag]
  GSE346319Homo sapiens3 个样本2026-10-28

  Genetic susceptibility plays an essential role in prostate cancer (PCa) risk, while the functional mechanisms underlying several classic risk loci remain largely uncharacterized. Here, we identified a PCa specific super-enhancer within 1q42.3 locus, termed NR125945-SE. Through comparative H3K27ac ChIP-seq analysis, we observed that NR125945-SE is highly active in PCa cells compared to normal controls. NR125945-SE contributes to PCa malignant progression. Mechanistically, integrative analysis combining RNA-seq and 4C-seq data revealed that NR125945-SE regulates the expression of CAPN2 and KRT19 through long-range chromatin interactions. Furthermore, we demonstrated that NR125945-SE activity is mediated by the cooperative binding of multiple transcription factors. In summary, our findings provide insights into a functional epigenetic element within a classic genetic risk locus, proposing a mechanism by which super-enhancer-mediated regulation promotes prostate cancer progression.
• Super-enhancer NR125945 drives prostate cancer malignancy via long-range chromatin interactions [4C-Seq]
  GSE346318Homo sapiens3 个样本2026-10-28

  Genetic susceptibility plays an essential role in prostate cancer (PCa) risk, while the functional mechanisms underlying several classic risk loci remain largely uncharacterized. Here, we identified a PCa specific super-enhancer within 1q42.3 locus, termed NR125945-SE. Through comparative H3K27ac ChIP-seq analysis, we observed that NR125945-SE is highly active in PCa cells compared to normal controls. NR125945-SE contributes to PCa malignant progression. Mechanistically, integrative analysis combining RNA-seq and 4C-seq data revealed that NR125945-SE regulates the expression of CAPN2 and KRT19 through long-range chromatin interactions. Furthermore, we demonstrated that NR125945-SE activity is mediated by the cooperative binding of multiple transcription factors. In summary, our findings provide insights into a functional epigenetic element within a classic genetic risk locus, proposing a mechanism by which super-enhancer-mediated regulation promotes prostate cancer progression.
• A High-Throughput Functional 3D Droplet Microfluidic Platform for Function-to-Transcriptome Profiling Identifies Candidate lncRNAs Associated with Engineered NK Cell Function
  GSE343647Homo sapiens12 个样本2026-10-28

  Background: Natural killer (NK) cell–based immunotherapies show considerable promise for cancer treatment; however, their efficacy against solid tumors remains limited by functional heterogeneity and the restrictive tumor microenvironment. Engineered NK cells, including mesothelin-directed chimeric antigen receptor cytokine- induced memory-like (MSLN-CAR CIML) NK cells, exhibit enhanced cytotoxic potential, yet the transcriptional programs underlying effective tumor killing remain poorly defined. Although protein-coding regulators of NK cell function have been extensively studied, the contribution of long non-coding RNAs (lncRNAs) to cytotoxic NK cell states remains largely unexplored, particularly in engineered NK cell therapies. Methods: To address this gap, we developed and applied a three-dimensional (3D) Matrigel-based droplet microfluidic screening platform that enables single-cell resolution analysis of NK–tumor interactions. Unlike conventional bulk transcriptomic approaches, this function-to-transcriptome workflow enables functional isolation of killer and non-killer NK-cell populations prior to transcriptomic profiling enabling the direct comparison of transcriptional programs associated with cytotoxic function while minimizing confounding effects of bulk population analyses. Using this approach, we profiled donor-matched MSLN-CAR CIML NK cells and CIML NK controls from three independent donors. Results: Comparative transcriptomic analysis revealed widespread differences in lncRNA expression between killer and non-killer NK cell populations, characterized predominantly by broad lncRNA downregulation that was consistently observed across donors and more pronounced in MSLN-CAR CIML NK cells than in CIML controls. Integrated lncRNA-mRNA analyses prioritized candidate lncRNA–gene pairs based on genomic proximity and coordinated co-expression patterns, identifying several lncRNAs associated with cytotoxic gene programs. These transcriptional signatures were further associated with enrichment of cytotoxic and inflammatory pathways characteristic of highly functional NK cell states. Conclusions: Together, these findings demonstrate the utility of our functional droplet microfluidic screening platform in prioritizing candidate lncRNAs associated with cytotoxic NK cell states within matrix-restricted tumor environments. By integrating functional phenotyping with transcriptomic profiling, this platform provides a framework for identifying candidate lncRNA and other potential biomarkers associated with cytotoxic NK states for future mechanistic validation and the rational optimization of NK cell–based immunotherapies for solid tumors.

  单细胞
• Hypoxia-Driven CA2 Promotes Trophoblast Dysfunction in Preeclampsia
  GSE342874Homo sapiens6 个样本2026-10-28

  Objective: Explore the potential function of Carbonic Anhydrase 2 (CA2) in the pathophysiology of preeclampsia. Methods: Peripheral blood and placental samples were collected from healthy pregnant women and patients with preeclampsia. Placental CA2 expression was validated in independent clinical cohorts and experimental mouse models. HTR-8/SVneo cells was cultured and transfected with a CA2 overexpression plasmid to evaluate trophoblast dysfunction. Bulk RNA sequencing was performed to identify downstream genes associated with CA2 overexpression, followed by VEGFA rescue experiments. Hypoxia-related regulation of CA2 was investigated. Lipid nanoparticle (LNP)-encapsulated siRNA against CA2 was constructed in an L-NAME-induced PE model to evaluate therapeutic effects. Results: CA2 expression was significantly increased in placental tissues and maternal serum from women with PE and was also elevated in experimental PE mouse models.CA2 predominantly localized in trophoblast cells, and correlated positively with serum creatinine and urea and correlated negatively with fetal birth weight. CA2 overexpression markedly suppressed trophoblast proliferation, migration, and invasion, without affecting apoptosis. Transcriptomic analysis suggested that vascular endothelial growth factor A (VEGFA) acted as a downstream mediator of CA2, and VEGFA overexpression partially rescued CA2-induced trophoblast dysfunction. CA2 expression was upregulated under hypoxic conditions and regulated by hypoxia-inducible factor-1α (HIF-1α). LNP-mediated CA2 silencing partially improved placental structure and fetal outcomes in vivo. Conclusion: CA2 is upregulated in the preeclamptic placenta and is associated with placental dysfunction and adverse fetal outcomes. Mechanistically, CA2 may act downstream of HIF-1α and contribute to trophoblast dysfunction partly through modulation of VEGFA signaling, and CA2 silencing partially improved maternal and fetal outcomes, highlighting CA2 as a potential therapeutic target for preeclampsia.