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。

• Baseline immune transcriptional states predict future HIV-1 acquisition in individuals at risk of sexual infection
  GSE352331Homo sapiens104 个样本2026-10-31

  Natural resistance to HIV-1 acquisition in highly exposed seronegative (HESN) individuals suggests the existence of pre-existing host states associated with reduced susceptibility. However, the baseline molecular determinants of susceptibility remain poorly understood. We analyzed PBMC transcriptomes by RNA sequencing in 104 HIV-1-seronegative men who have sex with men (MSM) at high risk of sexual exposure, including 65 HESN and 39 who subsequently seroconverted. Differential expression, functional enrichment, and spatial genomic clustering analyses were integrated with Elastic Net regularized logistic regression. HESN individuals showed enrichment of sensory receptor (p.adj=2×10⁻¹⁶) and cell-adhesion pathways (p.adj=9×10⁻³), together with non-random genomic clustering (p.adj=1×10⁻⁴) of differentially expressed genes at immune-related loci, including TCR, IGH, KIR, and MHC/HLA regions. In contrast, future seroconverters exhibited increased mRNA metabolism (p.adj=1.5×10⁻¹⁴), immune activation (p.adj=0.01), and type I interferon signaling (p.adj=0.02). A 14-gene risk score showed an out-of-fold AUC of 0.888. Cross-cohort transportability was evaluated in an independent ectocervical RNA-seq dataset. Applied without refitting, the signature showed moderate discrimination between long-term HESN and HIV-negative women at high risk of acquisition (AUC=0.689). The out-of-fold molecular risk score was also associated with time to HIV-1 seroconversion in MSM (log-rank p=7.1×10⁻¹¹; score×time interaction p=0.0086). These findings identify distinct pre-infection transcriptional states associated with HIV-1 acquisition and support partially transportable transcriptional architecture across blood and genital mucosal compartments.

  空间转录组
• Longitudinal Gene Expression Profiling Reveals Molecular Evolution and Transcriptional Reprogramming During Multiple Myeloma Relapse
  GSE352244Homo sapiens105 个样本2026-10-31

  This study aims to characterize gene expression alterations associated with multiple myeloma (MM) relapse by performing longitudinal gene expression profiling (GEP) of CD138+ plasma cells isolated from bone marrow mononuclear cells collected from 35 patients at baseline, first relapse, and second relapse.
• Transcription directs the migration of meiotic recombination intermediates [CC-Seq]
  GSE346184Saccharomyces cerevisiae114 个样本2026-10-31

  During meiosis, genetic diversity arises from the resolution of branched DNA intermediates called Holliday junctions to create crossovers—sites of reciprocal exchange between parental chromosomes. Holliday junctions arise during the repair of Spo11-induced DNA breaks, yet the principles linking break formation, repair, and chromosome architecture remain unclear. Top3, a type IA topoisomerase, acts on Holliday junction-containing recombination intermediates, but its spatiotemporal dynamics are unknown. Here, we map Top3 catalytic activity throughout meiotic prophase with strand specificity and nucleotide resolution. We identify a DNA sequence motif associated with catalysis and a pattern of activity around Spo11 hotspots that requires ongoing repair and Top3’s helicase partner, Sgs1. Strikingly, Top3 activity shifts over time, influenced by transcription, cohesin, and the crossover factors Msh5 and Mer3, redistributing toward sites of convergent transcription—known locations of enhanced meiotic cohesin association. Upon prophase exit, as crossovers are resolved, Top3 activity subsides. Remarkably, maps of genome-wide recombination reveal that crossover frequency is elevated at these same regions of convergent transcription. Collectively, we propose that Top3 tracks the transcription-directed migration of Holliday junction-containing meiotic recombination intermediates from Spo11 hotspots towards cohesin-associated axis sites, where crossover resolution occurs, promoting accurate meiotic chromosome segregation.
• Immune activation during broadly neutralizing antibody-mediated HIV suppression prior to post-intervention control
  GSE344609Homo sapiens52 个样本2026-10-31

  Broadly neutralizing antibodies (bNAbs) have been associated with enhancement of HIV-specific T or B cell responses and sustained partial control of HIV replication in some people with HIV (PWH). The mechanisms through which bNAbs may potentiate host immunity in this context are not known. We previously reported the outcomes of a clinical trial in which ten PWH on antiretroviral therapy (ART) received a combination of immunotherapies including two bNAbs administered immediately preceding an analytic treatment interruption (ATI). After bNAb levels waned, seven participants exhibited varying degrees of post-intervention control of HIV linked to a robust expansion of activated CD8+ T cells in response to rebounding virus. To investigate the role of the bNAbs in enhancing endogenous immune responses, we looked for evidence of HIV-specific or broader immune activation during the period after ART was paused and prior to rebound when bNAbs were controlling HIV replication. At a timepoint early post-ART interruption and at least one month before virus emerged in plasma, we detected an increase in levels of plasma inflammatory proteins as well as phenotypic and transcriptional activation of innate and adaptive immune cells. Compared to non-controllers, post-intervention controllers demonstrated unique transcriptional activation patterns as well as differential longitudinal plasma inflammatory protein trends. No enhancement of HIV-specific T cell or antibody responses was observed in this window. This study identifies activated cell types and inflammatory pathways that are recruited early during bNAb-mediated HIV suppression and that may play a role in potentiating long-lasting HIV immune control after bNAb therapy.
• Microglia modulate concussion biomarkers and recovery in male mice
  GSE330926Mus musculus55 个样本2026-10-31

  There is a critical unmet need for concussion biomarkers that predict cognitive recovery. Existing TBI biomarkers largely capture acute cellular damage rather than the multicellular repair processes that determine long-term outcome, and whether microglia causally shape divergent trajectories remains unclear. Here, we used PLX5622 to deplete microglia and other CSF1R-dependent myeloid cells in a male mouse model comparing concussion alone to concussion preconditioned by prior subconcussive impacts. Microglial depletion had no effect on cognitive outcome after concussion alone, but introduced a significant novel object recognition deficit specifically when concussion was preconditioned, revealing a history-dependent role for microglia in recovery. To identify the molecular substrates of this divergence, we profiled brain-derived GluA1/2 + extracellular vesicle (EV) miRNAs and single-nuclei transcriptomes from the injured brain. Diagnostic and injury-history EV miRNA biomarkers discriminated between concussion subtypes in microglia-intact animals but lost this discriminative power after depletion, indicating that these neuron-enriched biomarkers are influenced by microglia-dependent biology rather than injury alone. snRNA-seq further revealed that microglial depletion selectively induced transcriptional programs related to oligodendrocyte maturation after unconditioned concussion, a candidate substrate for this microglia-dependence. Finally, we identified a serum EV miRNA panel that estimated cognitive recovery across injury conditions. Together, these findings identify a history-dependent role for microglia in concussion outcome and characterize brain-derived EVs as a potentially promising tool for surveilling the neuroinflammatory processes influencing recovery.

  单细胞
• Nuclear Argonaute HRDE-1 Maintains Chromatin-Independent Transcriptional Silencing through a Transgenerational Small RNA Feedback Loop
  GSE312413Caenorhabditis elegans174 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Nuclear Argonaute HRDE-1 Maintains Chromatin-Independent Transcriptional Silencing through a Transgenerational Small RNA Feedback Loop [nuclear CUT&Tag]
  GSE311921Caenorhabditis elegans90 个样本2026-10-31

  Epigenetic inheritance of transcriptional silencing is traditionally attributed to chromatin-based mechanisms in which Argonaute–small RNA complexes recruit histone-modifying enzymes. Here we show that, in Caenorhabditis elegans, the nuclear Argonaute HRDE-1 maintains germline transcriptional repression independently of canonical heterochromatin marks. Using inducible, germline-specific HRDE-1 depletion combined with nuclear sorting, CUT&Tag, and nascent transcription profiling, we identify a functionally defined subset of endogenous genes, pseudogenes, and repetitive elements that become transcriptionally activated upon loss of HRDE-1 despite retaining H3K9me3, H3K23me3, and H3K27me3. HRDE-1 directly restrains RNA polymerase II (Pol II) while simultaneously promoting polyUG-dependent amplification of antisense 22G-RNAs in perinuclear condensates, thereby coupling nuclear transcriptional repression to small RNA biogenesis. HRDE-1 loss causes progressive erosion of 22G-RNAs and delays silencing re-establishment, revealing a transgenerational feedback loop in which small RNAs, and not chromatin modifications, constitute the primary heritable signal. These findings redefine nuclear Argonautes as active drivers of RNA-based epigenetic inheritance and broaden our understanding of how small RNA pathways maintain transcriptional silencing across generations.
• 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.
• HFpEF HMDP: ventricular RNA-seq in an expanded BXD strain panel
  GSE348752Mus musculus194 个样本2026-10-30

  Systems genetics strategy across multiple Hybrid Mouse Diversity Panel (HMDP) cohorts. RNA sequencing of ventricles from HFpEF mice was performed primarily in an expanded panel of BXD strains, together with a small number of classic inbred strains. This submission represents the expanded BXD component of the HFpEF HMDP project.
• Late-gestation heat stress induces gene expression and persistent DNA methylation changes in the mammary gland parenchyma at birth and weaning
  GSE346246Bos taurus64 个样本2026-10-30

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Time series analysis of transcriptomic responses to iron and zinc stress in Poplar
  GSE344088Populus trichocarpa173 个样本2026-10-30

  Extending our understanding of iron (Fe) and zinc (Zn) homeostasis beyond annual model plants is essential for improving plant productivity, nutritional quality, and food safety. However, the mechanisms coordinating metal acquisition, systemic signaling, and detoxification remain poorly understood in woody perennials. We generated a 21-d time-series multi-omics resource integrating transcriptomic, ionomic, and physiological measurements from roots and leaves of black cottonwood (Populus trichocarpa) exposed to Fe or Zn deficiency or excess. Temporal analyses revealed tissue-specific metal partitioning, extensive nutrient crosstalk, and restriction of Zn accumulation during prolonged Zn excess. Gene regulatory network inference identified bHLH38/39.2 as a hub associated with root Fe uptake and leaf Fe signaling. Fe deficiency rapidly induced five C-TERMINALLY ENCODED PEPTIDE (CEP) genes in roots. A fluorescently labeled CEP peptide supplied to roots accumulated in leaves, where CEP treatment induced IRON MAN (IMA) genes. Receptor-dependent protoplast assays further demonstrated CEP-mediated activation of IMA promoters. These findings support a model in which root-derived CEP peptides convey Fe status to leaf IMA signaling. Under Zn excess, declining Zn accumulation coincided with increased root suberization and induction of suberin-biosynthetic genes. NAC058.1 and NAC058.2 emerged as regulatory hubs and activated most tested suberin gene promoters. These findings suggest that NAC-regulated suberization restricts Zn entry during prolonged exposure. Our study identifies systemic and barrier-based mechanisms of micronutrient homeostasis in a woody perennial.

  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.
• 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.
• FACT depletion results in a temporal cascade of chromatin disruption preceding transcriptional dysfunction in stem cells [CUT&Run]
  GSE319809Mus musculus193 个样本2026-10-30

  The histone chaperone FACT is essential for chromatin organization and stem cell identity, yet how it preserves chromatin integrity over time remains unclear. We generated a high-resolution temporal map of events leading to chromatin destabilization and cell identity loss in murine embryonic stem cells following rapid dTAG-mediated depletion of FACT. Loss of FACT initiates a rapid cascade, with loss of H3K4me3 and disruption of nucleosome phasing at the 5′ ends of active genes beginning within 10 minutes. This architectural destabilization permits pluripotency transcription factors to ectopically occupy gene bodies in a transcription-dependent manner. Epigenomic disruptions result in stalled RNA Polymerase II occupancy and altered H3K36me3 deposition preceding a global transcriptional collapse at 2 hours of FACT depletion. Together, these findings define a temporal hierarchy in which epigenomic failure precedes and drives transcriptional dysfunction, revealing that continuous FACT activity is required to prevent progressive deterioration of chromatin architecture.
• Acute Degradation of Pumilio Proteins Reveals a Biphasic Posttranscriptional Regulatory Hierarchy in Embryonic Stem Cell Fate Decision [RNA-Seq]
  GSE310694Mus musculus84 个样本2026-10-30

  Post-transcriptional regulation is critical for mammalian embryogenesis yet has been underexplored. We previously showed that RNA-binding Pumilio proteins (Pum1/2) are essential for early mouse embryogenesis and embryonic stem cell (ESC) functions. Here, using acute protein degradation systems combined with time-resolved RNA-seq and eCLIP, we delineate a two-phase regulatory hierarchy modulated by Pum1/2 in mouse ESCs. The first phase, occurring within 10 hours of Pum1/2 depletion, is predominantly the stabilization of over 100 Pum1/2-target mRNAs, while the second phase, occurring in subsequent 66 hours, propagates to over 1,000 mRNAs mostly through indirect regulatory effects. Functionally, Pum1/2 depletion delays transition from naïve to formative pluripotency, impairs neuroectoderm differentiation, and enhances germline specification. Mechanistically, Pum1/2 directly repress mRNAs encoding PRC2 subunits, including Suz12, thereby constraining H3K27me3 deposition at neuroectodermal gene loci. These findings establish Pum1/2 as biphasic post-transcriptional regulators of pluripotency and lineage balance and link RNA stability control to chromatin-mediated silencing.
• iPSC-derived antigen-presenting cells engineered to express IL12 stimulate tumor-tissue reprogramming and antitumor immunity
  GSE303722Homo sapiens; Mus musculus64 个样本2026-10-30

  Activation of cancer-reactive T cells by dendritic cells (DCs) is important for cancer elimination by host immunity. One type of cancer immunotherapy in which DCs loaded with "cancer antigens" are administered has not been able to achieve stable efficacy due to heterogeneity in cell quality dependent on patient DC status. We constructed IL12-producing antigen-presenting cells from mouse induced pluripotent stem cells (iPSC). These cells can be controlled to proliferate using cytokines, allowing for the mass production of cells with stable performance. When these cells were loaded with a model cancer antigen and administered to cancer-bearing mice, cancer-reactive T cells rapidly acquired effector functions and propagated an interferon (IFN)-stimulated gene signature to cancer tissue distant from the site of administration. This was accompanied by infiltration of effector cells into the cancer tissue, while associated with a decrease in myeloid-derived suppressor cells. These were extremely more potent than immune checkpoint inhibitors (ICIs) and were further amplified in combination with ICIs and correlated with antitumor effects. Based on these observations, we constructed IL12-producing antigen-presenting cells from human iPSCs that express only HLA molecules involved in cancer antigen presentation and exclude other HLA molecules for improved versatility. These human cells, like their mouse counterparts, were capable of cytokine-regulated proliferation and induced antigen-specific activation and IFN-γ production of cancer antigen-specific T cells. Thus, these cells may become an alternative antigen-presenting cell platform for patient DCs to overcome HLA polymorphisms and ensure stable supply and quality.
• Bidirectional Plant-Microneedle Responses to Guide Biomaterial Design
  GSE279492Solanum lycopersicum58 个样本2026-10-30

  Designing biomaterials compatible with plants and specific payloads enables new technologies for precision agriculture, including targeted and dose‐controlled agrochemical delivery that overcomes the runoff, drift, and cuticular exclusion limiting conventional methods. However, broader implementation requires a systematic understanding of the complex interactions among payloads, biomaterial properties, and plant responses to establish design principles that support a sustained biotic–abiotic interface. Using microneedles made of different polymers and microstructures, this study investigates plant–biomaterial interactions to develop effective compound delivery strategies. Biodegradation studies show that microneedle biomaterials impart distinct mechanical strength, hydrophilicity, and surface charge, influencing the release of bioactive cargo. Transcriptomic analyses reveal a largely shared acute response to microneedle injection, with some material‐ or structure‐dependent variation in immunity and metabolism. Mid‐term biochemical responses show corresponding differences in membrane integrity and antioxidant activity. Despite these responses, microneedle treatments caused minimal effects on plant growth, chlorophyll content, stomatal conductance, and quantum efficiency of photosystem II. Finally, we demonstrate how biomaterial properties influence agrochemical delivery using hydrophilic plant growth regulator gibberellic acid (GA3) and hydrophobic herbicide pelargonic acid (PA), into tomato and lettuce, respectively. These findings establish principles for engineering plant‐biomaterial interfaces to accommodate payloads with diverse characteristics while ensuring plant safety.
• 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).
• TFIIIC regulates SMC complex binding and 3D DNA contacts between tRNA genes
  GSE352553Caenorhabditis elegans94 个样本2026-10-28

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Drinking-Water 4,4'-Methylenedianiline Establishes a Longitudinally Tractable Mouse Model of Cholestatic Liver Injury
  GSE352312Mus musculus72 个样本2026-10-28

  This study examines time-dependent hepatic responses to 4,4'-methylenedianiline (MDA), a cholestatic hepatotoxicant, administered to male C57BL/6JJcl mice in drinking water. Liver RNA sequencing was performed in separate terminal cohorts sampled on Days 1, 2, 3, 4, and 8 after exposure to control tap water, thioacetamide (TAA; 300 mg/L), or MDA (750 mg/L). The dataset comprises 72 poly(A)-selected liver RNA-seq libraries and provides gene-level expression measurements for characterizing temporal transcriptional changes and comparing the MDA model with the TAA reference condition.
• Microregional RNA sequencing reveals layer-specific smooth muscle cell heterogeneity in human bicuspid aortic valve-associated aortic dilatation
  GSE329454Homo sapiens60 个样本2026-10-28

  BAV is associated with aortic dilatation that can progress to aneurysm. To detect layer-specific transcriptomic profiles in the human aortic media with BAV, we performed microregional RNA sequencing analysis.
• Bulk RNA-seq atlas of cytokine-polarized murinebone-marrow-derived macrophages (BMDMs) across inflammatory, regulatory, and reparative stimuli
  GSE315641Mus musculus81 个样本2026-10-28

  Macrophages are highly plastic immune cells that adopt diverse functional states in response to local microenvironmental cues. In tissues, they contribute to host defense, maintain homeostasis, and coordinate responses to perturbations such as infection, injury, and inflammation. This functional diversity arises from their ability to integrate signals from cytokines, growth factors, and stromal interactions, particularly during tissue damage when macrophages transition from inflammatory to regulatory and reparative states. Despite increasing recognition of macrophage heterogeneity, most transcriptomic studies of macrophage polarization focus on a limited set of stimuli, providing an incomplete view of the cytokine-driven programs that shape macrophage behavior during inflammation and repair. Key mediators, including IL-4, IL-13, IL-33, IL-6, IL-10, GM-CSF, and TGF-β, induce distinct yet partially overlapping transcriptional responses that give rise to specialized and hybrid macrophage states. However, a systematic comparative analysis of these cytokine-induced programs remains lacking. To address this gap, we performed bulk RNA-sequencing of murine bone marrow–derived macrophages stimulated in vitro with a comprehensive panel of cytokines representing inflammatory, regulatory, and reparative pathways. This dataset enables direct comparison of cytokine-specific transcriptional programs, delineates classical, alternative, and hybrid activation states, and provides a resource for studying the molecular basis of macrophage plasticity.

  扰动筛选细胞图谱
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [endoBID]
  GSE314423Homo sapiens96 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
• RNA sequence, structure, and cell type specific features drive pseudouridylation by PUS7 [incellBIDPool1]
  GSE314389Homo sapiens66 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
• Genomic and Immune Profiling Characterizes Immune Heterogeneity and a TIGIT-Associated Subtype in Intrahepatic Cholangiocarcinoma
  GSE350183Homo sapiens164 个样本2026-10-27

  Background and Aims: Intrahepatic cholangiocarcinoma (iCCA) is characterised by marked molecular and microenvironmental heterogeneity and moderate response to immunotherapy. We aimed to define the genomic and spatial determinants of immune checkpoint activity in iCCA and their association with clinical outcome. Approach and Results: We performed integrated transcriptomic, DNA panel sequencing, and multiplex immunohistochemistry analyses in a cohort of 144 patients with iCCA. Tumors were classified according to STIM-defined microenvironmental subtypes. Spatially resolved immune profiling was conducted across tumor core, stroma, invasive margin, and adjacent liver. Immune checkpoint expression, cellular proximity, and clinical outcome were analysed using Cox regression and Kaplan-Meier methods. TIGIThigh tumors were further characterised by differential gene expression and pathway enrichment analyses. STIM classification stratified tumors into inflamed (47%) and non-inflamed (53%) subtypes with distinct survival outcomes and genomic profiles. Recurrent alterations in CDKN2A/B, TP53, MTAP, and BAP1 showed subtype-specific enrichment and prognostic relevance. Spatial immune profiling revealed compartment-specific distributions of T cells and immune checkpoints, with predominance of TIGIT and PD-1 expression in stromal and marginal regions. Most tumor-infiltrating T cells lacked inhibitory receptor expression, while co-expression of multiple checkpoints was uncommon. TIGIThigh tumors displayed coordinated activation of immune effector, antigen presentation, and interferon signalling pathways, alongside enrichment of distinct genomic alterations, defining an immune-activated molecular subtype. Conclusions: Integrated genomic and spatial immune profiling reveals pronounced context-dependent heterogeneity of immune checkpoint regulation in iCCA. TIGIT delineates an immune-activated subtype with distinct molecular features, providing a potential biomarker framework for patient stratification and rational immunotherapeutic targeting.

  空间转录组
• VIPP1/pTAC4 indirectly supports PEP accumulation and RpoB occupancy on chloroplast DNA
  GSE339035Arabidopsis thaliana108 个样本2026-10-27

  Chloroplast DNA together with proteins and RNAs form nucleoids, where genomes are stored, replicated and expressed. VIPP1/pTAC4 is a conserved membrane-associated protein previously identified in chloroplast nucleoid fractions, suggesting a possible role of this protein in linking plastid DNA, thylakoid membranes, and transcription. Here, we used plastid ChIP-seq to test whether VIPP1/pTAC4 directly affects plastid-encoded RNA polymerase (PEP) association with chloroplast DNA. Loss of VIPP1/pTAC4 caused a genome-wide reduction in RpoB occupancy, but we found no evidence of VIPP1/pTAC4 binding to chloroplast DNA. Likewise, the VIPP1-interacting protein VIA1 did not detectably bind chloroplast DNA, but was not required for normal RpoB occupancy. Comparison with other non-photosynthetic mutants and immunoblot analyses indicated that reduced PEP occupancy in ptac4 is likely an indirect consequence of impaired chloroplast development and reduced PEP core subunit accumulation. These findings challenge a direct role of VIPP1/pTAC4 in the chloroplast nucleoid and highlight the pleiotropic effects of chloroplast biogenesis defects on plastid transcription.
• T and B cells recognize splicing-derived neutrophil neoantigens in lupus
  GSE327018Homo sapiens100 个样本2026-10-27

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Bulk RNA-seq of neutrophils from systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, and healthy control samples
  GSE326777Homo sapiens78 个样本2026-10-27

  This study profiled bulk RNA-seq from human neutrophil samples derived from individuals with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, and healthy controls. Total RNA was extracted and sequenced to characterize transcriptomic features across disease groups. Raw and normalized gene-level count matrices, gene annotation, and sample-level metadata are provided.
• Micropatterning for soma, proximal neurite, and distal neurite RNA profiling
  GSE352013Mus musculus59 个样本2026-10-26

  Transcripts are not evenly distributed along a dendrite, but transcriptome-wide profiling at defined positions is difficult because neurites in culture follow irregular paths. To address this, we developed micropatterned poly-D-lysine tracks to guide neurites from cultured mouse hippocampal neurons along a shared axis. Soma, proximal neurite, and distal neurite fractions, each pooled from several neurons, can then be collected separately and molecularly characterized, leveraging the shared geometry. The micropatterned and dissected subcellular fractions reproduced the known soma–neurite contrast, including the higher relative abundance of ribosomal transcripts in neurites, and showed modest separation between proximal and distal profiles. Whole-neuron profiles from micropatterned and standard cultures showed no coordinated genome-wide separation, although individual genes differed. Between the proximal and distal neurite fractions, most expressed genes were relatively less abundant distally; fifty-four ran counter to that proximal-to-distal gradient, with higher distal abundance in at least 10 of 12 matched sample sets. The photomask design, per-sample collection metadata, and compartment profiles provide a basis for position-resolved profiling along the neurite.
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses
  GSE351578Mus musculus68 个样本2026-10-26

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries