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。

• 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.
• 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
• 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.
• 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.
• 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.
• 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 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
• 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.
• 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
• 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.

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• 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.
• 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
• 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.
• 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.
• 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
• Development and preclinical evaluation of a decoy DLL4-encoding oncolytic HSV-1 for solid tumors
  GSE334438Homo sapiens12 个样本2026-10-28

  Preclinical and clinical investigation of oncolytic HSV-1 (oHSV) treatment for cancer has indicated increased Notch signaling in tumors after treatment. Since Notch activation often heralds cancer cell stemness, angiogenesis, and invasion, the induction of this pathway after oHSV virotherapy can support tumor growth and limit response to virotherapy. Here, we evaluated the impact of blocking DLL4, a Notch ligand, on virotherapy. Matched tumor biopsies pre- and post-oHSV (CAN-3110, NCT03152318) treatment revealed an induction of DLL4 post-therapy. We observed that expression of a recombinant soluble decoy DLL4 (sDLL4) could block Notch activation in tumor cells. Thus, we engineered an oHSV vector designed to encode for soluble DLL4 (OVsDLL4) to block DLL4-mediated signaling. RNA sequencing and gene set enrichment analysis revealed that, relative to control oHSV, OVsDLL4 blocked Notch and sprouting angiogenesis pathways after treatment. Despite slower virus replication in vitro, OVsDLL4 cytotoxicity remained effective against tumor cells. Transcriptome profiling also indicated a significant dysregulation of metabolic pathways related to oxidative phosphorylation and glutathione metabolism, in accordance with increased oxygen consumption observed by Seahorse analysis in cells expressing sDLL4. OVsDLL4-treated cells further showed increased reactive oxygen species relative to control oHSV-treated cells. Co-culture of infected tumor cells with macrophages revealed that OVsDLL4 treatment educated macrophage gene expression towards an inflammatory polarization. In vivo, the therapeutic efficacy of OVsDLL4 was underscored after treatment of mice bearing different solid tumors resulted in reduced tumor burden and prolonged survival.
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [ASO]
  GSE328887Homo sapiens40 个样本2026-10-28

  Pseudouridines are abundant mRNA modifications that can impact splicing, translation, and stability to tune gene expression. PUS7 is one of the major mRNA pseudouridine synthases whose dysregulation leads to neurodevelopmental disorders and cancer, underscoring the critical function of PUS7-dependent pseudouridines. Beyond a short and degenerate consensus sequence, the molecular mechanisms underlying PUS7-mediated pseudouridylation remain unknown. A lack of targeted, high-throughput pseudouridine detection methods limits simultaneous interrogation of PUS7 regulatory features across many experimental conditions. We developed novel Nanopore sequencing tools, including Nano-Mod-Amp, to reveal pseudouridine stoichiometry, its RNA structural context, and dependence on PUS7 levels at specific sites across biological conditions. We established that RNA sequence and structural features are important for efficient mRNA modification by PUS7. Perturbing structure through mutations or antisense oligos modulates pseudouridylation levels. Pseudouridines are largely responsive to PUS7 protein levels, demonstrating the regulatory potential of varying PUS7 levels across cellular conditions. Conversely, PUS7 activity is also regulated in a cell-type specific manner, independent of PUS7 expression levels in a manner consistent with regulation by RNA structure and RNA binding proteins. Together, we uncovered regulatory features guiding PUS7 activity using new Nanopore sequencing tools, enabling site specific modulation of PUS7-dependent pseudouridines. Our framework can be applied to other RNA-modifying enzymes to query the regulation of the epitranscriptome.

  扰动筛选
• ACSS2-Mediated Metabolic-Epigenetic Crosstalk Drives Fulvestrant Resistance and Represents a Novel Therapeutic Target
  GSE319879Homo sapiens12 个样本2026-10-28

  Endocrine therapies target hormone-dependent cancer cells, primarily through estrogen receptor alpha (ERα), expressed in ~70% of breast cancers (ER+). Despite treatment advances, 30-40% of ER+ breast cancer patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. We validated poor outcomes for liver metastasis patients treated with Fulvestrant (Fulv) using the local Carle Foundation Hospital cohort and examined metabolic pathways in liver metastatic patient-derived xenograft (PDX) models, revealing upregulated lipid and acetyl-CoA production. Our previous work demonstrated that combining Fulv with acetyl-CoA synthase inhibitor (ACSI) targeting Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2), synergistically reduced ER+ metastatic breast cancer (MBC) cell viability in vitro. Using multiple analytical approaches-isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing-we characterized the effects of acetyl-CoA synthesis inhibition on Fulv-induced alterations. Fulv treatment of MBC cells increased ACSS2 expression and acetate utilization. Isotope tracing revealed that Fulv decreased acetate flux to the TCA cycle while promoting fatty acid synthesis. Importantly, ACSS2 was predominantly nuclear and CUT&RUN sequencing showed that Fulv treatment increased ACSS2 chromatin occupancy and ERα/ACSS2/H3K27ac overlapping sites near genes associated with tumor progression, which was eliminated by combination of ACSI and Fulv. RNA sequencing revealed reduction of Fulv-induced expression of genes involved in cancer cell metabolism and key signaling pathways in cancer with the Fulv+ACSI combination. In a therapy-resistant xenograft model, combining Fulv and ACSI reduced Fulv-dependent increase in metastatic burden. Our findings indicate ACSS2 contributes to endocrine therapy resistance through nuclear acetyl-CoA provision for epigenetic alterations. Targeting these cancer cell adaptations represents a novel therapeutic approach potentially reducing metastasis-related mortality and improving breast cancer treatment outcomes.
• ACSS2-Mediated Metabolic-Epigenetic Crosstalk Drives Fulvestrant Resistance and Represents a Novel Therapeutic Target [RNA-Seq]
  GSE300550Homo sapiens18 个样本2026-10-28

  Endocrine therapies target hormone-dependent cancer cells, primarily through estrogen receptor alpha (ERα), expressed in ~70% of breast cancers (ER+). Despite treatment advances, 30-40% of ER+ breast cancer patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. We validated poor outcomes for liver metastasis patients treated with Fulvestrant (Fulv) using the local Carle Foundation Hospital cohort and examined metabolic pathways in liver metastatic patient-derived xenograft (PDX) models, revealing upregulated lipid and acetyl-CoA production. Our previous work demonstrated that combining Fulv with acetyl-CoA synthase inhibitor (ACSI) targeting Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2), synergistically reduced ER+ metastatic breast cancer (MBC) cell viability in vitro. Using multiple analytical approaches—isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing—we characterized the effects of acetyl-CoA synthesis inhibition on Fulv-induced alterations. Results showed increased ACSS2 expression and acetate utilization with Fulv treatment. Isotope tracing revealed that Fulv decreased acetate flux to the TCA cycle while promoting fatty acid synthesis, though fatty acid synthesis inhibition did not synergize with Fulv. Importantly, ACSS2 was predominantly nuclear for therapy-resistant cells, suggesting epigenetic regulation roles. CUT&RUN sequencing showed Fulv treatment increased global ACSS2 binding sites and ERα/ACSS2/H3K27ac overlapping sites, which combination ACSI+Fulv therapy completely eliminated. RNA sequencing revealed increased cell proliferation gene expression with Fulv treatment. Combination therapy reduced metastatic burden. Our findings indicate ACSS2 contributes to endocrine therapy resistance through nuclear acetyl-CoA provision for epigenetic alterations. Targeting these cancer cell adaptations represents a novel therapeutic approach potentially reducing metastasis-related mortality and improving breast cancer treatment outcomes.
• ACSS2-Mediated Metabolic-Epigenetic Crosstalk Drives Fulvestrant Resistance and Represents a Novel Therapeutic Target [CUT&Run]
  GSE300549Homo sapiens48 个样本2026-10-28

  Endocrine therapies target hormone-dependent cancer cells, primarily through estrogen receptor alpha (ERα), expressed in ~70% of breast cancers (ER+). Despite treatment advances, 30-40% of ER+ breast cancer patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. We validated poor outcomes for liver metastasis patients treated with Fulvestrant (Fulv) using the local Carle Foundation Hospital cohort and examined metabolic pathways in liver metastatic patient-derived xenograft (PDX) models, revealing upregulated lipid and acetyl-CoA production. Our previous work demonstrated that combining Fulv with acetyl-CoA synthase inhibitor (ACSI) targeting Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2), synergistically reduced ER+ metastatic breast cancer (MBC) cell viability in vitro. Using multiple analytical approaches—isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing—we characterized the effects of acetyl-CoA synthesis inhibition on Fulv-induced alterations. Results showed increased ACSS2 expression and acetate utilization with Fulv treatment. Isotope tracing revealed that Fulv decreased acetate flux to the TCA cycle while promoting fatty acid synthesis, though fatty acid synthesis inhibition did not synergize with Fulv. Importantly, ACSS2 was predominantly nuclear for therapy-resistant cells, suggesting epigenetic regulation roles. CUT&RUN sequencing showed Fulv treatment increased global ACSS2 binding sites and ERα/ACSS2/H3K27ac overlapping sites, which combination ACSI+Fulv therapy completely eliminated. RNA sequencing revealed increased cell proliferation gene expression with Fulv treatment. Combination therapy reduced metastatic burden. Our findings indicate ACSS2 contributes to endocrine therapy resistance through nuclear acetyl-CoA provision for epigenetic alterations. Targeting these cancer cell adaptations represents a novel therapeutic approach potentially reducing metastasis-related mortality and improving breast cancer treatment outcomes.
• ACSS2-Mediated Metabolic-Epigenetic Crosstalk Drives Fulvestrant Resistance and Represents a Novel Therapeutic Target [ATACSeq]
  GSE300548Homo sapiens12 个样本2026-10-28

  Endocrine therapies target hormone-dependent cancer cells, primarily through estrogen receptor alpha (ERα), expressed in ~70% of breast cancers (ER+). Despite treatment advances, 30-40% of ER+ breast cancer patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. We validated poor outcomes for liver metastasis patients treated with Fulvestrant (Fulv) using the local Carle Foundation Hospital cohort and examined metabolic pathways in liver metastatic patient-derived xenograft (PDX) models, revealing upregulated lipid and acetyl-CoA production. Our previous work demonstrated that combining Fulv with acetyl-CoA synthase inhibitor (ACSI) targeting Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2), synergistically reduced ER+ metastatic breast cancer (MBC) cell viability in vitro. Using multiple analytical approaches—isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing—we characterized the effects of acetyl-CoA synthesis inhibition on Fulv-induced alterations. Results showed increased ACSS2 expression and acetate utilization with Fulv treatment. Isotope tracing revealed that Fulv decreased acetate flux to the TCA cycle while promoting fatty acid synthesis, though fatty acid synthesis inhibition did not synergize with Fulv. Importantly, ACSS2 was predominantly nuclear for therapy-resistant cells, suggesting epigenetic regulation roles. CUT&RUN sequencing showed Fulv treatment increased global ACSS2 binding sites and ERα/ACSS2/H3K27ac overlapping sites, which combination ACSI+Fulv therapy completely eliminated. RNA sequencing revealed increased cell proliferation gene expression with Fulv treatment. Combination therapy reduced metastatic burden. Our findings indicate ACSS2 contributes to endocrine therapy resistance through nuclear acetyl-CoA provision for epigenetic alterations. Targeting these cancer cell adaptations represents a novel therapeutic approach potentially reducing metastasis-related mortality and improving breast cancer treatment outcomes.
• RNA sequencing of HeLa cells infected with CHIKV and CHIKV mutant virus
  GSE299154Homo sapiens12 个样本2026-10-28

  The analysis indicates that CHIKV 6K/TF R37S infection leads to changes in genes related to endoplasmic reticulum stress, and KEGG analysis also enriched pathways related to endoplasmic reticulum stress in biological metabolism. Meanwhile, CHIKV TF ΔPBM infection causes changes in genes related to ion transport, and KEGG analysis has enriched pathways related to biological metabolism that are associated with sugar metabolism