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。

• A Single-Cell Atlas of Human Periodontal Ligament During Orthodontic Tooth Movement
  GSE327337Homo sapiens5 个样本2026-10-31

  Orthodontic tooth movement (OTM) requires coordinated remodeling of the periodontal ligament (PDL) and alveolar bone, yet the cellular architecture underlying this process in human tissues remains incompletely understood. Here, we generated the first single-cell transcriptomic atlas of the human PDL during OTM by profiling cells from the pressure and tension sides of teeth collected at day 3 and day 7 following force application. This atlas reveals the major stromal and immune cell populations and highlights spatial and temporal heterogeneity across force conditions and remodeling stages.

  单细胞空间转录组细胞图谱
• Endogenous PD-L1-Blocking Antibodies Drive Potent Anti-Tumor Immunity
  GSE326633Homo sapiens27 个样本2026-10-31

  Checkpoint blockade therapy, though transformative, remains ineffective in 70-80% of patients, with autoimmune adverse effects. Here, we provide the first evidence of a naturally occurring form of immune checkpoint blockade mediated by endogenous antibodies that functionally replicate the effects of therapeutic checkpoint inhibitors, without autoimmune symptoms. Through cloning and reconstructing patient-derived monoclonal antibodies, we show that certain cancer patients produce PD-L1-blocking antibodies that can restore T cell function and induce potent anti-tumor immunity. Broad polyreactive responses to multiple checkpoints confer no survival advantage. However, patients who are selectively positive for PD-L1 antibodies exhibit prolonged survival, tumors enriched with memory T cells, and activated circulating T cells. Mechanistically, these PD-L1 antibodies block PD-1/PD-L1 interactions and restore T cell function, in vitro and in vivo, revealing a naturally regulated form of checkpoint inhibition. Our data reveal that key principles of successful immunotherapy can emerge endogenously in a subset of patients, redefining our understanding of immune competence, tolerance, and therapeutic responsiveness in cancer, offering a mechanistic framework to explain how certain patients mount more effective anti-tumor immunity.
• Upregulated TRPM1 is associated with apoptosis in Rs1 knockout mice and in ARPE19 cells through increased intracellular calcium
  GSE326551Homo sapiens8 个样本2026-10-31

  The pathological mechanism underlying retinal apoptosis in X-linked retinoschisis (XLRS), a disease caused by retinoschisin 1 (RS1) deficiency, remains incompletely understood. This study aimed to investigate the role of transient receptor potential melastatin 1 (TRPM1) in retinal tissues and cells. Retinal function and structure were assessed by electroretinography (ERG) and optical coherence tomography (OCT). Protein expression was evaluated by immunofluorescence staining and western blotting (WB). Retinal morphology was examined by hematoxylin and eosin (H&E) staining. Apoptotic retinal cells were detected by TUNEL staining. Key proteins were screened using proteomics data obtained by mass spectrometry. Intracellular calcium levels were measured using Rhod-2 AM. TRPM1 expression in Rs1-KO mice was 1.3-fold higher than that in wild-type mice (p < 0.05), whereas TRPM1-overexpressing ARPE19 cells exhibited approximately twofold higher expression than the empty vector control group. Mechanistically, TRPM1-mediated calcium influx promoted calcium/calmodulin-dependent protein kinase II (CAMKII) phosphorylation. Concomitantly, the accumulation of the autophagy-related proteins P62 and LC3B, increased BAX expression, and decreased BCL2 expression were observed in both Rs1-KO retinal tissues and TRPM1-overexpressing ARPE19 cells. These findings collectively suggest that TRPM1 may contribute to cell’s apoptosis. Our study provides new insight into the mechanism of retinal apoptosis in XLRS.
• Small RNA sequencing of fibrotic intestinal tissues from TNBS-induced mice
  GSE326149Mus musculus10 个样本2026-10-31

  To investigate miRNA expression changes associated with intestinal fibrosis, we performed small RNA sequencing on colon tissues from TNBS-induced fibrotic mice and control mice. This dataset was generated to identify fibrosis-associated miRNAs and provide a basis for subsequent functional and mechanistic studies of intestinal fibrosis.
• mRNA expression profiling of intestinal fibrosis in TNBS-induced mice
  GSE326147Mus musculus10 个样本2026-10-31

  To characterize transcriptomic alterations associated with intestinal fibrosis, we performed mRNA sequencing on colon tissues from TNBS-induced fibrotic mice and control mice. This dataset was generated to identify differentially expressed genes and signaling pathways involved in intestinal fibrosis.
• Comparative study of the osseointegration capacity of porous tantalum, titanium, and HA/PA66
  GSE325408Mus musculus9 个样本2026-10-31

  Obtaining long-term and stable osseointegration of biomaterials in vivo remains a significant challenge. In recent years, pure titanium, HA/PA66, and porous tantalum have been widely used in the field of orthopedic implants. However, there is no comparative study of these three materials in the field of osseointegration. In this study, the physical properties, biosafety, osteogenic differentiation, and osseointegration of these three materials were comparatively investigated through material characterization, in vitro experiments, and in vivo experiments. In vitro experiments showed that porous tantalum has the roughest surface and better hydrophilicity, which is more conducive to osteoblast adhesion, proliferation, and differentiation. In vivo experiments confirmed that porous tantalum has the best osseointegration effect after implantation in vivo, with more surrounding new bone tissue and higher bonding strength. The results of this study are of great significance in guiding the improvement of biomaterials and promoting the selection of materials for practical clinical applications.
• Somatic TP53 Mutations Drive T and NK Cell Dysfunction and Create an Inflammatory Immune Niche in Acute Myeloid Leukemia
  GSE324592Homo sapiens2 个样本2026-10-31

  TP53-mutant acute myeloid leukemia (AML) is characterized by poor prognosis and limited response to immunotherapy, yet the mechanisms underlying immune failure in this setting remain unclear. Here, we integrate single-cell DNA sequencing with surface proteomics to demonstrate that somatic TP53 mutations arise not only in leukemic blasts but also in T and NK cells from patients with TP53-mutant AML. TP53-mutant T cells exhibit enhanced exhaustion phenotypes, impaired cytotoxic function, and altered clonal architecture. Mechanistically, mutant p53 reprograms T cells toward a pro-inflammatory yet dysfunctional state, reshaping cytokine networks and promoting a niche enriched in inflammatory and myeloid-supportive signals. These mutant T cells impair both intrinsic effector function and the functionality of surrounding immune cells. Introduction of TP53 mutations into healthy donor T cells recapitulates exhaustion and impaired tumor control, whereas elimination of mutant p53 restores effector function, normalizes cytokine programs, and improves disease control in a TP53-mutant AML xenograft model.

  单细胞
• Priapulids polarize the recurrent genomic evolution of ecdysozoans
  GSE324316Halicryptus spinulosus; Priapulus caudatus19 个样本2026-10-31

  Priapulids constitute a key lineage for understanding the early ecdysozoan evolution, as their phylogenetic position, slow rates of evolution, and rich Cambrian fossil record contrasts with the highly derived nature of arthropods and nematodes. Here, we report chromosome-scale genomes for two priapulids and show that they did not experience the accelerated genomic evolution prevalent in other ecdysozoans suggesting this acceleration occurred recurrently across multiple branches rather than once. suggesting it did not arise once but occurred recurrently in multiple lineages. This recurrent trend involves the dislocation and rearrangement of ancestral chromosomal units and extensive gene loss, repeatedly affecting essential functions such as ciliary motility and cell division. We further uncover an ancestral whole genome duplication in priapulids; preferential expression of retained paralogues during introvert formation suggests this duplication contributed to priapulid emergence and radiation during the Cambrian. Recurrent loss of ancestral genomic characters during the evolution of Ecdysozoa parallels convergent morphological simplification, such as miniaturisation
• RNA-seq of Mus musculus 2-cell embryos (WT vs Tcl1 KO) with CDCA treatment
  GSE323388Mus musculus14 个样本2026-10-31

  This study includes paired-end bulk RNA-seq data generated from Mus musculus embryos at the 2-cell stage. Samples comprise wild-type (WT) and Tcl1 knockout (KO) embryos, with and without CDCA treatment, with biological replicates. Raw sequencing data are available in SRA and linked here via SRA Run accessions.
• Enhanced plasmin generation due to PAI-1 deficiency impairs regulated vascular endothelial cell motility.
  GSE320323Homo sapiens6 个样本2026-10-31

  Background: Plasminogen activator inhibitor-1 (PAI-1) plays a crucial role in the plasminogen activation system and fibrinolysis. Congenital PAI-1 deficiency in humans is characterized by severe bleeding and delayed wound healing, which is consistent with the altered regulation of the fibrinolytic regulation. Although plasmin influences various cellular processes, the mechanisms by which PAI-1-mediated control of plasminogen activation and regulates endothelial cell (EC) behavior, especially at the pericellular level, are not well understood. The aim of this study was to elucidate the specific cellular effects of enhanced plasminogen activator (PA) activity caused by PAI-1 deficiency in human ECs. Methods: PAI-1 deficient human ECs (PAIKO-ECs) were generated using CRISPR/Cas9-mediated gene editing and compared them with wild-type ECs (WT-ECs). We investigated the impact of plasminogen-induced pericellular plasmin activity and its impact on endothelial migration and angiogenic tube formation, conducting additional transcriptomic analysis. Results: PAIKO-ECs exhibited markedly increased PA activity, as demonstrated by elevated plasmin generation in the presence of plasminogen. In scratch assays, PAIKO-ECs exhibited increased overall uncoordinated motility with multidirectional migration trajectories and impaired directional wound closure in the presence of plasminogen; however, cell proliferation remained unaffected. This aberrant migratory phenotype was reversed by aprotinin, recombinant active PAI-1, or the lysine analog epsilon-aminocaproic acid (EACA). EACA notably reduced plasminogen accumulation on the cell surface while preserving fluid-phase plasmin generation. This indicates that enhanced EC motility is driven by pericellular rather than fluid-phase plasmin activity. In tube formation assays, PAIKO-ECs formed a higher number of extremities and branches, a phenotype that was reversed to the level of WT-ECs by EACA or aprotinin. Transcriptome analyses revealed differential gene expression related to fibrinolysis, angiogenesis, and endothelial-mesenchymal transition. Conclusions: These findings reveal that pericellular plasmin activity is essential for EC motility and angiogenic behavior under PAI-1-deficient conditions. This provides novel mechanistic insight into the spatial plasminogen activation systems in vascular remodeling.

  空间转录组
• A PolyQ Repeat in PIF7 acts as a tunable thermosensor in Arabidopsis [RNA-seq]
  GSE318452Arabidopsis thaliana3 个样本2026-10-31

  Plant growth is a highly plastic response requiring the integration of endogenous and environmental signals. Organisms from different climates must adapt to different temperature ranges, but the mechanisms by which proteins can alter their temperature response profile are not well understood. Central regulators of growth are the PHYTOCHROME INTERACTING FACTOR (PIF) family of bHLH transcription factors that activate the transcription of genes encoding auxin biosynthesis enzymes in response to temperature (thermomorphogenesis). Enhanced auxin levels direct cell elongation and growth. PIF7 is necessary for thermomorphogenesis, but it is not known how temperature activates PIF7. We have identified a critical role for a polyglutamine (polyQ) sequence in PIF7 that is necessary for PIF7 dimerization and DNA binding in response to temperature. We show that higher temperatures directly increase dimerization of PIF7 via the polyQ and thermal responsiveness is proportional to the polyQ length. We are able to use this thermosensory module to create synthetic transcription factors and confer temperature dependency on independent developmental decisions such as the specification of stomata. Extensive variation in the polyQ repeat length in different species suggests a mechanism to tune responsiveness to climate.
• A PolyQ Repeat in PIF7 acts as a tunable thermosensor in Arabidopsis
  GSE318393Arabidopsis thaliana4 个样本2026-10-31

  Plant growth is a highly plastic response requiring the integration of endogenous and environmental signals. Organisms from different climates must adapt to different temperature ranges, but the mechanisms by which proteins can alter their temperature response profile are not well understood. Central regulators of growth are the PHYTOCHROME INTERACTING FACTOR (PIF) family of bHLH transcription factors that activate the transcription of genes encoding auxin biosynthesis enzymes in response to temperature (thermomorphogenesis). Enhanced auxin levels direct cell elongation and growth. PIF7 is necessary for thermomorphogenesis, but it is not known how temperature activates PIF7. We have identified a critical role for a polyglutamine (polyQ) sequence in PIF7 that is necessary for PIF7 dimerization and DNA binding in response to temperature. We show that higher temperatures directly increase dimerization of PIF7 via the polyQ and thermal responsiveness is proportional to the polyQ length. We are able to use this thermosensory module to create synthetic transcription factors and confer temperature dependency on independent developmental decisions such as the specification of stomata. Extensive variation in the polyQ repeat length in different species suggests a mechanism to tune responsiveness to climate.
• Comparative profiling of SARS-CoV-2 variant infections reveals diverse impacts on host cell RNA and RNA binding protein distribution and regulation
  GSE318110Homo sapiens14 个样本2026-10-31

  RNA viruses perturb cellular RNA metabolism to promote viral transcript expression and genome replication. However, the extent of host cell RNA reprogramming and the consequences on RNA binding protein (RBP) expression and localization remain poorly understood. Here, we utilized an integrated set of transcriptomics, proteomics, and high-content imaging approaches to compare the impact of different SARS-CoV-2 variants, including an early viral isolate and later emerging variants of concern (Alpha, Delta and Omicron) on the host cellular RNA and RBP landscapes. While all variants deeply remodelled the host transcriptome in a subcellular compartment-specific manner, we found that Omicron variants express lower levels of viral RNA products compared to earlier variants, while still driving efficient production of viral proteins. The surge in viral RNA expression correlated with altered subcellular RNA biotype distribution, cytoplasmic mRNA exclusion, the selective disruption of the localization of polyA-tail interacting proteins, and the nuclear accumulation of non-coding transcripts such as RN7SL family members and MALAT-1. Unexpectedly, we found many RBPs that exhibiting altered subcellular localization following abiotic innate immune stimulation with poly(I:C) but remained unaltered in cells infected with SARS-CoV-2 variants, revealing a capacity for these viruses to limit the overall impact on the RBP subcellular distribution. Our results further indicate that Omicron infection sustains higher expression levels of proteins components of the signal recognition particle and translation factors, which may enable a more effective production of immune response and viral components. Altogether, this work highlights the deep impact of SARS-CoV-2 infection on host cell RNA regulatory landscape and provides new insights to explain the differential impact of Omicron compared to early SARS-CoV-2 variants.

  扰动筛选
• Regenerative macrophages from human iPSCs promoted vascular remodeling in human atherosclerotic organoid model
  GSE317284Homo sapiens26 个样本2026-10-31

  Recent studies have revealed that macrophages exhibit greater phenotypic diversity than the traditional M1/M2 classification, enabling them to display distinct functional properties depending on the surrounding microenvironment. Accordingly, it has become increasingly important to more finely characterize and evaluate macrophage subtypes that may operate within specific disease microenvironments. In this study, we aimed to identify a macrophage phenotype with therapeutic potential for atherosclerosis using an atherosclerosis-induced blood vessel organoid (BVO) model. To assess the effects of diverse macrophage phenotypes on the atherosclerosis, iPSC-derived macrophages (iMac) were generated and polarized into multiple phenotypic states. The polarized iMac populations displayed distinct gene expression profiles and exhibited functional differences in angiogenesis and regeneration related assays. For therapeutic evaluation, iPSC-derived BVOs were established and then induced to develop atherosclerotic features. During co-culture with the atherosclerotic BVO model, iPSC-derived regenerative macrophages (iMac R) showed active interactions with the organoids and produced therapeutic benefits on lipid clearance, anti-inflammatory responses, and regenerative effects. Notably, iMac R demonstrated superior therapeutic efficacy compared with other polarized macrophage phenotypes, highlighting their potential as a novel cell-based therapeutic strategy for atherosclerosis.
• ReprogRAM nanoplatform for direct conversion of fibroblasts into reprogrammed osteoblasts for bone regeneration
  GSE315875Homo sapiens4 个样本2026-10-31

  mRNA-based direct conversion offers an integration-free route for osteogenic cell-fate reprogramming, yet efficient reprogramming typically requires sustained expression of reprogramming factors. Here, we develop ReprogRAMs (Reprogrammable RNA Assemblies for Multi-factor expression), a self-assembled concatemeric mRNA nanoparticles synthesized by rolling-circle transcription and engineered for cap-independent translation. A single delivery of ReprogRAM to human dermal fibroblasts enabled cytosolic expression that persisted over time with minimal cytokine induction. By leveraging this long-acting expression profile, we encoded the osteogenic reprogramming factors Oct4 and Cbfβ and implemented a hybridized delivery strategy to enforce co-expression of both factors. ReprogRAM induced robust osteogenic conversion, as evidenced by increased mineralized matrix deposition, induction of osteoblast markers, and transcriptomic remodeling toward osteoblasts. Finally, transplantation of ReprogRAM-derived reprogrammed osteoblasts (rOBs) embedded in a gelatin scaffolds promoted bone repair in a critical-sized mouse calvarial defect model. Together, ReprogRAM provides a long-acting, integration-free mRNA modality for in situ cell-fate engineering and bone regeneration.
• Complement C3-Mediated Hippocampal CA2 Synaptic Impairments Underlie Social Deficits by Srpx2 Deficiency in Maternal Immune Activation
  GSE315602Mus musculus6 个样本2026-10-31

  Social behavior deficits are hallmark features of neurodevelopmental disorders. The hippocampal CA2 region and complement system are critical for social function and neurodevelopment. Here, we show SRPX2 interacts with complement protein C1Q and regulates complement-coagulation pathways, specifically downregulating C3 in astrocytes. Srpx2 deficiency induces transient C3 upregulation and selective excitatory synapse loss in hippocampal CA2 during adolescence. Moreover, Srpx2 deficiency and prenatal maternal immune activation interact to disrupt social behavior, accompanied by enhanced C3 expression and excitatory synapse loss in CA2. Our findings identify SRPX2 as a key regulator of complement-mediated synaptic function in CA2, providing insights into the molecular mechanisms underlying neurodevelopmental disorder-related social deficits.
• CRISPR screen after venetoclax and azacitidine treatment in AML cells
  GSE314297Homo sapiens12 个样本2026-10-31

  CRISPR screen was performed in three isogenic MOLM-13 acute myeloid leukemia (AML) cell lines (p53 WT/p53 R248Q/p53 KO) to analyze gene dependencies changes after treatment with venetoclax and azacitidine.

  扰动筛选
• Transciptomics analysis: the role of chronic ethanol feeding in promoting dysfunction of stromal vascular cells from rat viceral adipose tissue
  GSE312640Rattus norvegicus8 个样本2026-10-31

  Chronic ethanol exposure induces adipose tissue dysfunction. Rats are divided into 2 groups: CONT and ET. The study aim to determine the role of stromal vacular cells (SVC) in mediating viceral adipose tissue (VAT) dysfunction in alcohol-associated liver disease.
• 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.
• Nuclear Argonaute HRDE-1 Maintains Chromatin-Independent Transcriptional Silencing through a Transgenerational Small RNA Feedback Loop [Whole worm CUT&Tag]
  GSE311918Caenorhabditis elegans16 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.
• Nuclear Argonaute HRDE-1 Maintains Chromatin-Independent Transcriptional Silencing through a Transgenerational Small RNA Feedback Loop [small RNA-seq]
  GSE311555Caenorhabditis elegans28 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.
• Nuclear Argonaute HRDE-1 Maintains Chromatin-Independent Transcriptional Silencing through a Transgenerational Small RNA Feedback Loop [nuclear GRO-seq]
  GSE311554Caenorhabditis elegans8 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.
• Nuclear Argonaute HRDE-1 Maintains Chromatin-Independent Transcriptional Silencing through a Transgenerational Small RNA Feedback Loop [nuclear RNA-seq]
  GSE311553Caenorhabditis elegans20 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.
• Nuclear Argonaute HRDE-1 Maintains Chromatin-Independent Transcriptional Silencing through a Transgenerational Small RNA Feedback Loop [bulk RNA-seq]
  GSE311522Caenorhabditis elegans12 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.
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2 induced gene expression
  GSE311192Mus musculus27 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2 induced gene expression [Cut & Run]
  GSE311187Mus musculus15 个样本2026-10-31

  Transcription factor Foxp3, with its singular role in differentiation and function of regulatory T (Treg) cells in physiologic and inflammatory settings, is thought to act by modulating transcriptional responses to activatory extracellular cues including pro-inflammatory cytokines. However, the underlying mechanisms remain largely unknown. After Foxp3 is induced during Treg differentiation upon STAT5 activation downstream of interleukin-2 receptor (IL-2R), sustained STAT5 signaling facilitates fitness and suppressive capacity of mature Treg cells. We found that Foxp3 and phospho-STAT5 (pSTAT5) form a stable transcriptional complex. Upon IL-2 sensing, Foxp3 is recruited in a pSTAT5-dependent manner to GAS-motif-enriched cis-regulatory elements that are developmentally primed by STAT5 in Treg precursors prior to Foxp3 expression. Using chemogenetically and pharmacologically induced protein degradation, we demonstrate that Foxp3 modulates STAT5 signaling in activated Treg cells to selectively modulate their transcriptional response to IL-2, most prominently involving a Myc-dependent gene module. Our studies suggest that direct Foxp3-STAT5 cooperativity fine-tunes STAT5 signaling downstream of IL-2 receptor activation to support functionality of differentiated Treg cells.
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2 induced gene expression [RNA-Seq]
  GSE311182Mus musculus12 个样本2026-10-31

  Transcription factor Foxp3, with its singular role in differentiation and function of regulatory T (Treg) cells in physiologic and inflammatory settings, is thought to act by modulating transcriptional responses to activatory extracellular cues including pro-inflammatory cytokines. However, the underlying mechanisms remain largely unknown. After Foxp3 is induced during Treg differentiation upon STAT5 activation downstream of interleukin-2 receptor (IL-2R), sustained STAT5 signaling facilitates fitness and suppressive capacity of mature Treg cells. We found that Foxp3 and phospho-STAT5 (pSTAT5) form a stable transcriptional complex. Upon IL-2 sensing, Foxp3 is recruited in a pSTAT5-dependent manner to GAS-motif-enriched cis-regulatory elements that are developmentally primed by STAT5 in Treg precursors prior to Foxp3 expression. Using chemogenetically and pharmacologically induced protein degradation, we demonstrate that Foxp3 modulates STAT5 signaling in activated Treg cells to selectively modulate their transcriptional response to IL-2, most prominently involving a Myc-dependent gene module. Our studies suggest that direct Foxp3-STAT5 cooperativity fine-tunes STAT5 signaling downstream of IL-2 receptor activation to support functionality of differentiated Treg cells.
• RNA sequencing to compare SAIPS-PAI0 group with VIPS-PAI group
  GSE309777Rattus norvegicus2 个样本2026-10-31

  14 days after the VIPS-PAI and SAIPS-PAI0 scaffolds were implanted in the rat femoral defect models, tissues surrounding and within the scaffolds were harvested from both groups for RNA sequencing to analyze the gene expression profiles.
• Accurate In Vitro Recapitulation of Bile and Blood Partitioning of Drug Metabolites Using a hepatocyte culture system with induced open-form bile canaliculus icHep
  GSE307757Homo sapiens16 个样本2026-10-31

  Systemically circulating drug metabolites can cause organ damage, and there are species differences in the both the types of metabolites formed and their partitioning into bile and blood. Thus, it is necessary to evaluate the formation and biliary excretion of hepatic drug metabolites using in vitro evaluation system using human hepatocytes. Conventional sandwich-cultured hepatocytes (SCHs), however, form closed bile canaliculi that preclude direct collection of biliary excreted metabolites. Here, we assessed whether primary cultured hepatocytes with induced open-form bile canaliculus (icHep) provide a suitable system for evaluating the partitioning of drug metabolites produced in hepatocytes between bile and blood. Human hepatocytes derived from human liver–chimeric mice were cultured on claudin-1–coated plates, which facilitated the formation of open bile canalicular lumina, confirmed by co-immunostaining for MRP2 and ZO-1. RNA-seq analysis revealed that the expression levels of representative pharmacokinetics-related genes in icHep were comparable to those in SCHs. Following the addition of parent drugs to the blood-side chamber, metabolites were successfully collected from both blood- and bile-side chambers. Ziprasidone sulfoxide and mycophenolic acid glucuronide were predominantly recovered on the blood side, whereas celecoxib carboxylic acid and SN-38 glucuronide were preferentially excreted into bile. The metabolite partitioning observed in icHep was consistent with human in vivo data. In conclusion, icHep enables a quantitative evaluation of the hepatic disposition of drug metabolites including partitioning into bile and blood in human and represents a physiologically relevant in vitro system for human pharmacokinetic studies.