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。

• eCLIP-seq profiling of Flag-OTUD6B-associated RNA in HEK293T cells
  GSE352643Homo sapiens4 个样本2026-10-30

  RNA associated with Flag-OTUD6B was profiled by enhanced crosslinking and immunoprecipitation sequencing (eCLIP-seq) in human HEK293T cells. Two independent biological replicates were represented by two FLAG immunoprecipitation libraries and two corresponding size-matched input (SMInput) control libraries. This experiment and the OTUD6B-knockdown Ribo-seq experiment in MDA-MB-231 cells belong to the same research study.
• Ribosome profiling of OTUD6B knockdown and scramble-control MDA-MB-231 cells
  GSE352635Homo sapiens4 个样本2026-10-30

  Ribosome profiling was performed in human MDA-MB-231 cells with shOTUD6B-41 or a scramble-control shRNA. Two independent biological replicates were included per group, yielding four paired-end sequencing libraries. Gene-level read counts and FPKM expression values were generated. This experiment and the Flag-OTUD6B eCLIP-seq experiment in HEK293T cells belong to the same research study.

  扰动筛选
• Cilengitide limits the progression of both syndromic and sporadic thoracic aortic aneurysms by targeting alpha V integrins
  GSE352523Homo sapiens11 个样本2026-10-30

  Spatial transcriptomics was used to characterize gene expression patterns in human ascending aortic tissue from healthy controls, patients with Marfan syndrome (MFS), and patients with sporadic thoracic aortic aneurysm (sTAA). Carnoy-fixed, paraffin-embedded ascending aortic tissue sections were profiled using the 10x Genomics Visium platform. Spatially resolved gene expression profiles were analyzed to investigate transcriptional heterogeneity, pathway-associated signatures, and inferred cellular composition across disease groups.

  单细胞空间转录组
• Effects of orexin-A on human dermal papilla cells
  GSE352146Homo sapiens6 个样本2026-10-30

  We examined effects of orexin-A on human dermal papilla cells.
• Adaptive transcriptional responses to KRAS(G12C) inhibition in cancer cells
  GSE352065Homo sapiens60 个样本2026-10-30

  KRAS(G12C) inhibitors have demonstrated promising antitumor activity, but adaptive resistance remains a major therapeutic challenge. To characterize transcriptional adaptations to KRAS(G12C) inhibition, we performed bulk RNA sequencing of four human KRAS(G12C)-mutant cancer cell lines (H358, Calu-1, H23, and H1792) following treatment with RMC-6291. Transcriptomic analyses were conducted to identify treatment-associated gene expression changes and biological pathways, with particular emphasis on metabolic reprogramming and glutathione-associated responses. This dataset provides insights into the transcriptional responses of cancer cells to KRAS(G12C)-targeted therapy.
• StrataChip: a microphysiological system to capture dynamic keratinocyte fate and mechanical transitions during human epidermal morphogenesis
  GSE351999Homo sapiens1 个样本2026-10-30

  Epidermal development and homeostasis require precise coordination between keratinocyte differentiation and mechanics. Still, the mechanisms integrating these processes remain poorly understood in part due to limitations of existing experimental systems. Here, we introduce StrataChip, a tractable microphysiological system that enables dynamic, multimodal interrogation of human epidermal morphogenesis. The platform integrates a media perfused dermal tissue with human epidermal keratinocytes within a microfluidic device and supports rapid epidermal stratification following establishment of an air-liquid interface. High-resolution confocal imaging and single-cell RNA-sequencing demonstrate that the StrataChip recapitulates key architectural and molecular features of human epidermis, including distinct basal, spinous, and granular layers defined by canonical differentiation markers and adhesion molecule organization. Single-cell profiling reveals transcriptionally distinct basal and spinous subpopulations, including transitional states associated with suprabasal commitment. Live 3D imaging in situ captures keratinocyte morphodynamics including basal cell delamination and asymmetric division in early stages of epidermal stratification. Altogether, StrataChip provides a robust platform that is capable of dynamic and mechanistic interrogation of how gene regulation and cell mechanical changes are coupled during epidermal morphogenesis.

  单细胞
• T cell responses distinguish the subset of oral dysplasia that progressed to cancer
  GSE351967Homo sapiens16 个样本2026-10-30

  The factors that determine which oral premalignant lesions progress to cancer while others do not remain unclear. Immune responses to early lesions result in cancer immunoediting, so variability in their nature and strength may influence risk of cancer progression. Here, we show that T cell-mediated immune responses arise in oral premalignant dysplasia years before invasive cancer develops and distinguish lesions that progress from those that do not. Progressing lesions were characterized by robust infiltration of CXCL13+ CD8 T cells in proximity to dysplastic epithelial cells and macrophages expressing interferon-stimulated genes (ISGs), including the T cell-recruiting chemokines CXCL9, CXCL10, and CXCL11. Infiltrating CXCL13+ CD8 T cells were clonally expanded and persisted through malignant transformation. Over time, their frequency and transcriptional profile remained stable, while myeloid cells accumulated and basal epithelial cells upregulated an extracellular matrix-associated transcriptional program partly induced by IFNγ. The transition to invasive cancer was subsequently marked by tissue remodeling accompanied by a shift of the CXCL13+ CD8 T cells from the epithelium to the underlying stroma. Our results provide evidence that IFNγ-driven immune signatures are detectable early and distinguish progressing oral lesions.
• Elucidation of the anti-neuroinflammatory effect of M4FQA in HMC3 cells
  GSE351949Homo sapiens12 个样本2026-10-30

  These study demonstrate that M4FQA attenuates LPS-induced microglial inflammation through coordinated modulation of NF-κB-associated transcriptional networks and suggest that interaction with the TLR4/MD-2 system may contribute to its anti-inflammatory activity. M4FQA therefore emerges as a promising CQA-derived therapeutic candidate for further investigation in the treatment of neuroinflammatory disorders. Pretreatment of 1µM M4FQA significantly attenuated LPS-induced expression of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Transcriptomic analysis demonstrated that pretreatment of M4FQA markedly modulated the LPS-induced transcriptional profile, with prominent regulation of genes associated with NF-κB-related inflammatory signaling, cytokine and chemokine responses, cellular homeostasis, and MAPK-associated pathways. M4FQA also reduced the expression of NF-κB-associated inflammatory chemokines, including CCL2, CXCL8, and CXCL6, while functional analyses identified additional modulation of genes associated with synaptic organization and signaling. Molecular docking predicted favourable interaction of M4FQA with the TLR4/MD-2 complex, and SPR analysis further supported interaction with the TLR4 target.
• Transcriptomic profiling of human nucleus pulposus cells following Mulberrin treatment
  GSE351312Homo sapiens6 个样本2026-10-30

  This study profiled the transcriptomes of human nucleus pulposus cells with or without Mulberrin treatment to identify gene expression changes associated with Mulberrin exposure. genes and exploring molecular pathways potentially involved in the cellular responses to Mulberrin treatment.
• GPS2 attenuates cigarette smoke-induced airway epithelial injury by attenuating mitochondrial oxidative stress
  GSE347944Homo sapiens6 个样本2026-10-30

  Cigarette smoke (CS) exposure contributes to airway epithelial injury and mitochondrial dysfunction in chronic obstructive pulmonary disease (COPD). G protein pathway suppressor 2 (GPS2) is involved in mitochondrial-nuclear communication, but its role in cigarette smoke-induced airway epithelial injury remains unclear. In this study, transcriptome sequencing was performed to investigate the molecular changes associated with GPS2 deficiency in airway epithelial cells and to explore the potential mechanisms linking GPS2 to mitochondrial dysfunction and epithelial injury. Combined with public transcriptomic data and experimental validation, our results suggest that reduced GPS2 expression is associated with alterations in energy metabolism, mitochondrial function, and redox homeostasis. These data provide a transcriptomic resource for further investigating the role of GPS2 in cigarette smoke-induced airway epithelial dysfunction.
• Ribosome profiling of clear cell renal cell carcinoma tumor and adjacent normal kidney tissue samples
  GSE346551Homo sapiens10 个样本2026-10-30

  Despite growing recognition that non-canonical open reading frame (ncORF)-encoded micropeptides constitute a hidden layebiological functions, and therapeutic relevance in renal cell carcinoma (RCC) remain entirely undefined. Through integrative transcriptomic, translatomic, and proteomic profiling of clinical RCC specimens, we systematically mapped the dysregulated ncORF-encoded micropeptidome and identified long non-coding RNAs (lncRNAs) as a predominant source of tumor-associated cryptic peptides. These findings illuminate a therapeutically actionable micropeptide-mediated regulatory network in RCC and establish ncORF-encoded tumor suppressors as a druggable class of biologics for precision oncology.r of functional regulators in cancer, their translational landscape,
• RNA-seq of clear cell renal cell carcinoma tumor and adjacent normal kidney tissue samples.
  GSE346548Homo sapiens10 个样本2026-10-30

  Renal cell carcinoma (RCC) is among the most common urological malignancies, yet the transcriptomic landscape underlying its pathogenesis remains incompletely characterized, particularly for non-coding regions that may harbor functional non-canonical open reading frames (ncORFs). Here we performed whole-transcriptome RNA-seq on 5 clear cell RCC tumor tissues and 5 adjacent normal kidney tissues to systematically profile mRNA, lncRNA, and circRNA expression. This dataset serves as the transcriptomic layer of an integrative multi-omics study aimed at identifying dysregulated ncORF-encoded micropeptides in RCC, with lncRNAs representing a predominant source of tumor-associated cryptic peptides. The data provide a reference for translational activity assessment when combined with matchedribosome profiling and immunopeptidomics datasets.

  多组学
• Mycobacterium abscessus inhibits IFNg activation, impairing control of intracellular infection
  GSE339253Homo sapiens80 个样本2026-10-30

  Mycobacterium abscessus (Mab) is an emerging pathogen among the nontuberculous mycobacteria (NTM), causing infections in individuals with lung conditions (e.g. cystic fibrosis) or immunodeficiency (e.g. impaired interferon gamma (IFNg) production or response pathway). Mab infections are difficult to treat, and adjunctive therapy with IFNg is sometimes used for refractory infections. However, the reasons that endogenous IFNg fails to control infections remain unknown. Using a THP-1 macrophage-mycobacteria infection model, we studied the combined effects of IFNg and imipenem (IPM) on intracellular M. abscessus. Through flow cytometry, RNAseq and cytokine measurements in infected cells treated for over 24 hours with IPM and IFNg alone or in combination, we identified distinct cellular response pathways at different stages of infection. In early stages of infection, IFNg pathway signaling, as assessed by STAT1 phosphorylation level, was preserved, while there were changes in TNFa, IL1b and IL6 inflammatory pathways in response to the infection. However, after 24 hrs of infection the IFNg signaling was impaired. Addition of imipenem abolished the impairment in IFNg signaling and led to a significant decrease in intracellular bacterial load. At 48 hrs, treatment with IFNg alone or combined with IPM significantly reduced the IFNg receptor1 surface display, while total cellular IFNgR1 and IFNgR2 levels remained unchanged. Mycobacterium abscessus reduces STAT1 phosphorylation and blunts IFNg signaling, thereby limiting macrophage activation and facilitating intracellular mycobacterial growth. Imipenem counteracts this suppression, reactivates antimicrobial pathways, enhances IFNg-mediated killing, and promotes bacterial clearance. Understanding M. abscessus immune subversion and how to counter it is crucial for developing effective antimicrobial therapies.
• RNA-bound MYBL2 engages the oncogenic transcription factors MAFG and FRA1 to promote melanoma
  GSE335104Homo sapiens9 个样本2026-10-30

  Non-mutational mechanisms, including copy number alterations and transcription factor dysregulation, are critical drivers of melanoma progression. We identify the transcription factor MYBL2 as a key oncogenic driver located on frequently amplified chromosome 20q. MYBL2 overexpression promotes transformation and correlates with poor survival, yet paradoxically, its transactivation function is dispensable for oncogenic activity. Instead, MYBL2 acquires a previously unrecognized non-canonical RNA binding function in melanoma cells enabled by the melanoma-associated RNA landscape. Through these RNA interactions, MYBL2 reshapes the chromatin landscape toward an AP-1 permissive state and promotes chromatin association of the oncogenic transcription factors MAFG and FRA1, indirectly reprogramming tumor-promoting gene networks whose expression predicts poor outcomes across multiple cancers. Importantly, disrupting the MYBL2-RNA interaction using a small decoy RNA impairs MYBL2 association with MAFG and FRA1 and suppresses melanoma cell growth. Our findings establish MYBL2 as an RNA binding-dependent, 20q gain-associated driver of melanoma and reveal that MYBL2-RNA interactions promote melanoma progression through chromatin and transcriptional network remodeling.
• Variable Imprinting of Hepatitis C Virus-Induced Chromatin Remodeling Following Viral Clearance [ChIP-Seq]
  GSE333673Homo sapiens49 个样本2026-10-30

  Background & Aims: Direct-acting antivirals (DAAs) have revolutionized Hepatitis C virus (HCV) care, allowing for high cure rates. However, the risk of Hepatocellular carcinoma (HCC) persists in a subset of patients even after sustained virologic response (SVR). Understanding the factors linking HCV infection to HCC risk, both before and after cure, may reveal novel HCC prevention strategies. We previously identified an HCV-induced ""epigenetic scar"" that can persist despite viral cure. Currently, it is unknown whether this epigenetic signature persists across all cured patients or if it exhibits significant inter-patient variability. This study aimed to characterize the heterogeneity of epigenetic reversion following SVR and to investigate whether the kinetics of viral clearance is a mechanism that is associated with this heterogeneity, by comparing different treatment regimens. Methods: To precisely evaluate epigenetic reversion while controlling for significant inter-patient variability in baseline chromatin landscapes, we analyzed a unique cohort of paired human liver biopsies (pre- and post-SVR) from patients treated with IFN-based therapies. To explore potential drivers of the observed heterogeneity, we utilized cell culture models treated with DAAs or varying concentrations of IFN to mimic rapid versus gradual viral elimination. Genome-wide H3K9ac ChIP-seq and RNA-seq were performed to characterize epigenetic and transcriptomic changes. The results were also validated with another histone modification, H3K27Ac, from HCV patients treated with IFN and DAA. Results: By normalizing post-treatment profiles to each patient's own baseline, we revealed heterogeneity in the trajectory of recovery. While some patients achieved extensive reversion of HCV-induced signatures, others retained a persistent H3K9ac footprint despite viral clearance. In cell culture models, distinct remodeling patterns were observed based on treatment kinetics: regimens inducing rapid viral clearance (DAA treatment or high-concentration IFN) were associated with greater persistence of the epigenetic signature. Conversely, gradual clearance (low-concentration IFN) coincided with more extensive reversion of H3K9ac modifications. Independent clinical validation confirmed these dynamics, showing that DAA-cured patients harbor a significantly stronger persistent H3K27ac signature compared to those cured by IFN. Conclusions: These results indicate that the host epigenome possesses a variable capacity for recovery that is distinct from virologic outcomes. Our data suggests that the kinetics of viral clearance may be a key determinant of this epigenetic plasticity, highlighting the need to look beyond SVR to understand the residual oncogenic environment of the cured liver.
• Diagnostic value of a panel of serum exosomal miRNAs as potential biomarkers for pancreatic cancer
  GSE332591Homo sapiens96 个样本2026-10-30

  Exosomes and exosomal miRNAs were isolated from the serum of patients with pancreatic cancer, cholangiocarcinoma, duodenal cancer, pancreatic benign tumor and healthy individuals. Exosomal miRNAs were analyzed using next-generation sequencing (NGS) to identify miRNA candidates for diagnosis.
• Aberrant stabilization of the m6A reader IGF2BP3 drives metastatic progression and 5-FU refractoriness in FBXW7-mutant colorectal cancer
  GSE327329Homo sapiens13 个样本2026-10-30

  FBXW7 is mutated in approximately 10% of colorectal cancers (CRC), and the vast majority of these alterations are loss-of-function mutations that abrogate its E3 ligase activity. Tumors harboring FBXW7 mutations frequently display aggressive clinical behavior, including enhanced metastatic dissemination and poor response to chemotherapy. However, the post-transcriptional regulatory axis downstream of FBXW7 loss has remained largely unexplored. In this study, we aimed to delineate the mechanistic link between FBXW7-dependent alterations in m6A RNA methylation and malignant phenotypic outcomes in CRC. We found that loss of FBXW7 markedly increased the protein abundance of the m6A reader IGF2BP3, and this effect was attributable to impaired GSK3β/FBXW7-dependent degradation of IGF2BP3. Mechanistically, FBXW7 promoted K63‐linked polyubiquitination and autophagy-mediated degradation of IGF2BP3, indicating that FBXW7 serves as a post-translational brake on IGF2BP3 stability. In FBXW7-deficient cells, IGF2BP3 preferentially bound cancer-promoting transcripts, including DPYD and COL4A1, and stabilized these mRNAs in an m6A-dependent manner. Functionally, IGF2BP3-mediated stabilization of DPYD and COL4A1 promoted epithelial to mesenchymal transition and increased resistance to 5-FU. In vivo, knockout of IGF2BP3 in FBXW7-deficient CRC models significantly reduced liver metastasis and chemoresistance to 5-FU, demonstrating that IGF2BP3 is a critical effector of the FBXW7-m6A axis. Collectively, these findings establish IGF2BP3 as a previously unrecognized post-transcriptional driver of metastasis and 5-FU refractoriness in FBXW7-mutant CRC, and suggest that therapeutic strategies aimed at disrupting IGF2BP3 stabilization or m6A-dependent IGF2BP3-mRNA interactions provides a rationale for therapeutic intervention in FBXW7-mutated CRC.
• Detection of a sequence feature for recursive splicing
  GSE327295Homo sapiens5 个样本2026-10-30

  RNA splicing is directed by cis-acting sequence signals interacting with trans-acting factors to remove introns from newly transcribed pre-mRNA, joining exons to generate mature mRNA. Splicing happens far more often than observed exon-exon junctions in mRNA. As one contributing process, the spliceosome progressively removes large introns in small segments by ‘recursive splicing’, instead of splicing the whole intron at one time. However, the cis-acting sequences associated with recursive splicing have not been identified. Using probabilistic mixture models, we found that recursive splicing occurs more frequently in first introns, which are typically longer, and exhibit a distinct CG-rich sequence feature in the sequences flanking the upstream 5’SS, and depletion of CGs in the downstream polypyrimidine tract. Remarkably, recursive splicing is also more frequent in downstream introns of genes containing first introns with these properties. Mechanistically, these data suggest that early events in RNA synthesis and processing influence the prevalence of recursive splicing for the rest of the transcript. Finally, we developed a sequence-dependent classifier for recursive splicing, which we tested with a novel medium-throughput primer extension assay. In summary, the usage of recursive splicing sites is established at the beginning of RNA synthesis through newly-identified sequence motifs flanking both ends of the first intron.

  计算与 AI
• Aberrant stabilization of the m6A reader IGF2BP3 drives metastatic progression and 5-FU refractoriness in FBXW7-mutant colorectal cancer
  GSE326794Homo sapiens4 个样本2026-10-30

  Loss of the E3 ubiquitin ligase FBXW7 leads to aberrant stabilization of the m6A reader IGF2BP3 in colorectal cancer. To identify the RNA targets of IGF2BP3 under FBXW7-deficient conditions, we performed HITS-CLIP-seq in isogenic DLD1 FBXW7 wild-type and knockout cell lines. CLIP-seq analysis revealed that IGF2BP3-binding sites were enriched in 3' UTR regions of protein-coding mRNAs, and that IGF2BP3 preferentially bound cancer-promoting transcripts including DPYD and COL4A1.
• Establishment of a multi-stage in vitro screening platform to identify candidate compounds for intestinal mucosal damage in inflammatory bowel disease
  GSE321659Homo sapiens9 个样本2026-10-30

  Mucosal healing is a key therapeutic goal in inflammatory bowel disease (IBD), which is characterized by mucosal lesions in the gastrointestinal tract. For IBD drug development, it is important to identify multiple compounds with strong effects on mucosal injury and different mechanisms of action. Here, we established an intestinal organoid-based assay to evaluate cytokine-induced inflammatory and epithelial stress responses. We also developed an intestinal microphysiological system (intestinal MPS)-based assay for quantitative evaluation of cytokine-induced changes in mucosal architecture. By integrating these assays, we constructed a multi-stage screening platform to identify candidate compounds that suppress inflammatory responses and preserve mucosal architecture. Tofacitinib, an approved IBD drug, showed positive effects in these assays, supporting the relevance of this platform. Although organoid-based screening identified pimitespib as a candidate compound, pimitespib did not improve mucosal architecture in the intestinal MPS. Consistently, pimitespib failed to restore mucosal morphology in an IBD mouse model. These findings suggest that combining intestinal organoids with an intestinal MPS may help identify candidate compounds that suppress inflammatory responses while preserving mucosal architecture.
• Cucumber-derived exosome-like nanovesicles promote diabetic wound healing via AKT-HO-1 signaling
  GSE318192Homo sapiens10 个样本2026-10-30

  This study investigates the therapeutic efficacy of Cucumis sativus-derived exosome-like nanovesicles (CELNs) in promoting diabetic wound healing. We identified CELNs as a superior candidate among Cucurbitaceae species for enhancing fibroblast function and modulating the wound microenvironment. RNA-seq analysis of CELN-treated human dermal fibroblasts reveals a significant upregulation of epigen (EPGN) and activation of the NRF2-mediated antioxidant pathway. Mechanistically, CELNs activate the EGFR–PI3K/AKT–NRF2 axis, which mitigates oxidative stress and accelerates cellular migration and proliferation. To ensure sustained delivery, a CELN-loaded hydrogel system was developed, which significantly enhanced re-epithelialization and collagen deposition in STZ-induced diabetic mice. Our findings demonstrate that CELNs offer a promising nanotherapeutic approach for managing chronic diabetic ulcers by targeting EGFR-mediated antioxidant signaling.
• A Cross-scale Causal Mapping Framework Pinpoints Macrophage Orchestrators of Balanced Arterial Development
  GSE317047Homo sapiens3 个样本2026-10-30

  This dataset contains single-cell RNA sequencing profiles of induced pluripotent stem cell (iPSC)-derived blood vessel organoids (BVOs) cultured under different macrophage co-culture conditions. The aim is to investigate the regulation of vascular maturation and arterial development by the immune system. The BVOs were cultured either alone or with two polarized populations of iPSC-derived macrophages: activated (MGL low) and regenerative (MGL high). Single-cell transcriptomic analyses revealed polarization-dependent transcriptional changes in vascular endothelial and perivascular cell populations. This dataset allows for the identification of candidate genes and signaling pathways associated with arterial specification, vessel stabilization, and vascular maturation in a human organoid model.

  单细胞
• RNA-seq and CRISPR screen after venetoclax and azacitidine treatment in AML cells
  GSE314299Homo sapiens30 个样本2026-10-30

  This SuperSeries is composed of the SubSeries listed below.

  扰动筛选SuperSeries
• The p38α MAPK-MK2 axis drives chemotherapy-mediated nuclear actin remodeling to promote ovarian cancer progression
  GSE311931Homo sapiens18 个样本2026-10-30

  We sequenced SKOV3 (EV), wild-type, and R62D cells treated with or without cisplatin.It is to figure out whether cisplatin and nuclear F-actin levels would affect the transcriptional profile.
• Transcriptomic response to TRIP12 knockdown and HSP90 inhibition in melanoma cells
  GSE306539Homo sapiens32 个样本2026-10-30

  Melanoma, as a typical cancer, is characterized by high mutational burden and rapid proliferation, both of which contribute to elevated proteotoxic stress and reliance on protein quality control systems. To model this, we used the melanoma cell lines Ma-Mel-102 (differentiated, MLANA- and MITF-expressing, ~1200 missense mutations) and Ma-Mel-94 (dedifferentiated, ~700 missense mutations). This study investigates the role of the E3 ubiquitin ligase TRIP12 in regulating proteostasis in melanoma, particularly under proteotoxic stress induced by inhibition of HSP90, a key molecular chaperone. This dataset provides RNA-seq transcriptomic profiles of Ma-Mel-94 and Ma-Mel-102 cells following siRNA-mediated TRIP12 knockdown, with or without HSP90 inhibition by 17-DMAG.
• 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
• HOXA9 reprograms 3D genome architecture to regulate oncogenic transcription in acute myeloid leukemia [CUT&RUN]
  GSE301083Homo sapiens31 个样本2026-10-30

  The hierarchical three-dimensional (3D) organization of chromatin underpins the spatial and temporal control of gene expression during development. This principle is exemplified by the Hox gene clusters, where dynamic topological architecture governs precise transcriptional activation. While disruption of chromatin organization at Hox genes is increasingly recognized in various human malignancies, the extent to which Hox genes themselves contribute to shaping 3D genome architecture remains poorly understood. In particular, it is unknown whether oncogenic overexpression of HOXA9—a highly conserved transcription factor and common downstream effector of diverse genetic alterations in acute myeloid leukemia (AML)—can actively reprogram chromatin topology. Here, we uncover a pivotal role for HOXA9 as a master regulator of 3D chromatin architecture in human AML. We demonstrate that HOXA9 orchestrates a leukemia-specific reconfiguration of chromatin topology. HOXA9 promotes the formation of leukemia specific topologically associating domains (TADs) and establishes long-range enhancer–promoter interactions essential for maintaining the leukemic transcriptional program. Perturbation of HOXA9 leads to widespread architectural collapse, marked by the dissolution of chromatin loops, disrupted enhancer communication, and silencing of critical leukemogenic genes. Furthermore, HOXA9-mediated chromatin looping occurs independently of CTCF. Instead, HOXA9 functions through the cohesin complex to facilitate higher-order genome organization, thereby functioning as a non-canonical architectural factor. Among its targets, we identify NHLRC2 as a HOXA9-associated loop gene essential for leukemic cell survival and proliferation. Collectively, these findings uncover a previously unappreciated architectural function of HOXA9 in modulating 3D genome organization and sustaining oncogenic gene expression in AML. More broadly, they suggest a mechanistic paradigm in which HOX transcription factors actively reprogram nuclear architecture to enforce lineage-specific or malignant gene expression programs.

  空间转录组扰动筛选
• 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.