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。

• Specification of bone marrow sinusoids requires TIE2-mediated positive feedback involving COUP-TFII and VEGFR3 [Tek_ecko P11bm]
  GSE342121Mus musculus6 个样本2026-10-31

  The bone marrow (BM) vascular network drives bone development and supports hematopoiesis, yet the mechanisms governing its specialized sinusoidal architecture remain poorly characterized. Here, we show that the angiopoietin receptor TIE2 is highly expressed by BM sinusoidal endothelial cells (BM_SECs), and its endothelial deletion triggers sinusoidal capillarization, characterized by reduced vessel diameter and aberrant mural cell coverage. Mechanistically, TIE2 insufficiency drives a downregulation of VEGFR3 in BM_SECs, while leaving hepatic sinusoidal VEGFR3 unaffected. Notably, BM sinusoidal VEGFR3 downregulation occurred within 48 hours of induced endothelial Tek deletion. RNA-sequencing revealed that TIE2 insufficiency downregulated pathways related to sinusoidal development, alongside an aberrant upregulation of arterial and angiogenic genes. We validated this phenotype using inducible Tek deletion specifically within VEGFR3+ SECs, or in mutant mice with the insufficiency of TIE2 ligand ANGPT1. Furthermore, endothelial deletion of the transcription factor Nr2f2 (COUP-TFII) recapitulated these defects, yielding reductions in BM sinusoidal TIE2 and VEGFR3 expression. Finally, induced endothelial deletion of Flt4 produced a similar phenotype of defective BM sinusoidal formation. Together, our findings demonstrate that ANGPT1/TIE2 and COUP-TFII form a reciprocal regulatory loop essential for coordinating BM sinusoidal specification by sustaining VEGFR3 expression.
• A Viral Replication Level-Dependent Continuum of Transcriptional and MicroRNA Reprogramming in HIV-1-Infected Microglia Links Productive Infection to Neurocognitive-Associated Gene Networks [RNA-seq]
  GSE341759Homo sapiens8 个样本2026-10-31

  Microglia are major targets of HIV-1 in the brain. Despite the effectiveness of antiviral therapy, infected microglia, including those containing a replication-defective provirus, can express viral RNA and proteins that contribute to neuroinflammation. However, the degree to which productive infection shapes the host response in microglia remains poorly defined. Using single cell RNA-seq of HIV-1-infected C20 microglia, we stratified cells by counts of HIV-1 reads with splice junctions into low- and high-infection groups, enabling us to resolve a graded rather than binary host transcriptional response. A core set of immune and cell-cycle pathways was induced regardless of infection level, but several programs reversed direction with increasing viral burden: interferon-α/γ and EMT/hypoxia signatures peaked at low infection, while high infection was marked by suppression of these signatures alongside induction of mTORC1/MYC signaling, ribosome biogenesis, RNA processing, and mitotic activity, accompanied by progressive loss of cytoskeletal, motility, and developmental gene programs. This pattern was reproduced in iPSC-derived microglia, supporting its generalizability beyond an immortalized line. Integration of differentially expressed miRNAs with differentially expressed genes from the low- and high-infection groups showing the canonical inverse miRNA-target relationship revealed miRNA/mRNA networks with strong representation of miRNAs previously implicated in HIV-1 replication (e.g., miR-33a-5p, miR-3065-3p) and in neurodegenerative and psychiatric disease (e.g., miR-107, let-7c-5p). These findings define a productive-infection-level continuum in microglial transcription, miRNA reprogramming, and identify candidate miRNA-mediated mechanisms, independent of the canonical Env/Nef/Tat pathway, by which HIV-1-infected microglia may contribute to neuroinflammation and neurocognitive impairment in people with HIV-1.

  单细胞
• A Viral Replication Level-Dependent Continuum of Transcriptional and MicroRNA Reprogramming in HIV-1-Infected Microglia Links Productive Infection to Neurocognitive-Associated Gene Networks [scRNA-seq]
  GSE341758Homo sapiens6 个样本2026-10-31

  Microglia are major targets of HIV-1 in the brain. Despite the effectiveness of antiviral therapy, infected microglia, including those containing a replication-defective provirus, can express viral RNA and proteins that contribute to neuroinflammation. However, the degree to which productive infection shapes the host response in microglia remains poorly defined. Using single cell RNA-seq of HIV-1-infected C20 microglia, we stratified cells by counts of HIV-1 reads with splice junctions into low- and high-infection groups, enabling us to resolve a graded rather than binary host transcriptional response. A core set of immune and cell-cycle pathways was induced regardless of infection level, but several programs reversed direction with increasing viral burden: interferon-α/γ and EMT/hypoxia signatures peaked at low infection, while high infection was marked by suppression of these signatures alongside induction of mTORC1/MYC signaling, ribosome biogenesis, RNA processing, and mitotic activity, accompanied by progressive loss of cytoskeletal, motility, and developmental gene programs. This pattern was reproduced in iPSC-derived microglia, supporting its generalizability beyond an immortalized line. Integration of differentially expressed miRNAs with differentially expressed genes from the low- and high-infection groups showing the canonical inverse miRNA-target relationship revealed miRNA/mRNA networks with strong representation of miRNAs previously implicated in HIV-1 replication (e.g., miR-33a-5p, miR-3065-3p) and in neurodegenerative and psychiatric disease (e.g., miR-107, let-7c-5p). These findings define a productive-infection-level continuum in microglial transcription, miRNA reprogramming, and identify candidate miRNA-mediated mechanisms, independent of the canonical Env/Nef/Tat pathway, by which HIV-1-infected microglia may contribute to neuroinflammation and neurocognitive impairment in people with HIV-1.

  单细胞
• A Viral Replication Level-Dependent Continuum of Transcriptional and MicroRNA Reprogramming in HIV-1-Infected Microglia Links Productive Infection to Neurocognitive-Associated Gene Networks [miRNA-seq]
  GSE341757Homo sapiens4 个样本2026-10-31

  Microglia are major targets of HIV-1 in the brain. Despite the effectiveness of antiviral therapy, infected microglia, including those containing a replication-defective provirus, can express viral RNA and proteins that contribute to neuroinflammation. However, the degree to which productive infection shapes the host response in microglia remains poorly defined. Using single cell RNA-seq of HIV-1-infected C20 microglia, we stratified cells by counts of HIV-1 reads with splice junctions into low- and high-infection groups, enabling us to resolve a graded rather than binary host transcriptional response. A core set of immune and cell-cycle pathways was induced regardless of infection level, but several programs reversed direction with increasing viral burden: interferon-α/γ and EMT/hypoxia signatures peaked at low infection, while high infection was marked by suppression of these signatures alongside induction of mTORC1/MYC signaling, ribosome biogenesis, RNA processing, and mitotic activity, accompanied by progressive loss of cytoskeletal, motility, and developmental gene programs. This pattern was reproduced in iPSC-derived microglia, supporting its generalizability beyond an immortalized line. Integration of differentially expressed miRNAs with differentially expressed genes from the low- and high-infection groups showing the canonical inverse miRNA-target relationship revealed miRNA/mRNA networks with strong representation of miRNAs previously implicated in HIV-1 replication (e.g., miR-33a-5p, miR-3065-3p) and in neurodegenerative and psychiatric disease (e.g., miR-107, let-7c-5p). These findings define a productive-infection-level continuum in microglial transcription, miRNA reprogramming, and identify candidate miRNA-mediated mechanisms, independent of the canonical Env/Nef/Tat pathway, by which HIV-1-infected microglia may contribute to neuroinflammation and neurocognitive impairment in people with HIV-1.

  单细胞
• GOLDEN: Gene expression and allele-informed decomposition for genetic heterogeneity in spatial transcriptomic data
  GSE341398Homo sapiens2 个样本2026-10-31

  Spatial transcriptomics (ST) enables exploration of cellular interactions, but current methods rely on pathologist annotation and face limitations in addressing genetic heterogeneity, where niches harbor non-clonal cells, as in placental or allograft tissues. To decipher such inter-individual heterogeneity in ST, we developed GOLDEN (Gene expression and allele-informed decomposition for genetic heterogeneity), an allele-aware multi-task network that encodes spot-level expression into shared latent representations. Incorporating allele features, it uses dual heads to classify spot identity (target, non-target, or mixed) and to estimate target fractions. For evaluation, we generated synthetic ST data via a Gamma-distribution model using semi-allogeneic single-cell profiles. On these synthetic benchmarks, GOLDEN achieved reliable deconvolution (Pearson's r = 0.977; MAE = 0.045) while maintaining consistent predictions across real-world STs, which were validated through genetic evidence.

  单细胞空间转录组计算与 AI
• The transcriptomic profile of wild-type HGC-27 cells treated with conditioned media from ANGPTL4-overexpressing or control HGC-27 cells
  GSE338826Homo sapiens4 个样本2026-10-31

  Given that ANGPTL4 is a secreted protein, we combined conditioned medium treatment with transcriptomic analysis to determine whether the activation of downstream signaling pathways by ANGPTL4 overexpression is dependent on its secretion.
• MORC2A is required for DNA methylation and H3K9me3 at retrotransposons in the male germline [smallRNA-seq]
  GSE335167Mus musculus6 个样本2026-10-31

  Transposable elements pose a particular threat to the germline, where their activation can compromise fertility and generate heritable mutations. In male germ cells, transposon silencing depends on repressive epigenetic states, including CpG methylation and H3K9me3. Here, we identify MORC2A as an essential regulator of transposon repression in the mouse male germline. Conditional deletion of Morc2a in primordial germ cells caused complete male infertility, testicular atrophy, germ cell loss and meiotic arrest. MORC2A-deficient testes displayed derepression of evolutionarily young retrotransposons, accompanied by DNA damage and apoptosis. Genome-wide profiling revealed loss of CpG methylation and H3K9me3 at these elements. Small RNA sequencing showed that piRNA biogenesis and ping-pong amplification remain largely intact. Together, these datasets identify MORC2A as a male germline chromatin regulator required for epigenetic silencing of young transposable elements.
• MORC2A is required for DNA methylation and H3K9me3 at retrotransposons in the male germline [EM-seq]
  GSE335165Mus musculus6 个样本2026-10-31

  Transposable elements pose a particular threat to the germline, where their activation can compromise fertility and generate heritable mutations. In male germ cells, transposon silencing depends on repressive epigenetic states, including CpG methylation and H3K9me3. Here, we identify MORC2A as an essential regulator of transposon repression in the mouse male germline. Conditional deletion of Morc2a in primordial germ cells caused complete male infertility, testicular atrophy, germ cell loss and meiotic arrest. MORC2A-deficient testes displayed derepression of evolutionarily young retrotransposons, accompanied by DNA damage and apoptosis. Genome-wide profiling revealed loss of CpG methylation and H3K9me3 at these elements. Small RNA sequencing showed that piRNA biogenesis and ping-pong amplification remain largely intact. Together, these datasets identify MORC2A as a male germline chromatin regulator required for epigenetic silencing of young transposable elements.
• MORC2A is required for DNA methylation and H3K9me3 at retrotransposons in the male germline [CUT&RUN]
  GSE335164Mus musculus7 个样本2026-10-31

  Transposable elements pose a particular threat to the germline, where their activation can compromise fertility and generate heritable mutations. In male germ cells, transposon silencing depends on repressive epigenetic states, including CpG methylation and H3K9me3. Here, we identify MORC2A as an essential regulator of transposon repression in the mouse male germline. Conditional deletion of Morc2a in primordial germ cells caused complete male infertility, testicular atrophy, germ cell loss and meiotic arrest. MORC2A-deficient testes displayed derepression of evolutionarily young retrotransposons, accompanied by DNA damage and apoptosis. Genome-wide profiling revealed loss of CpG methylation and H3K9me3 at these elements. Small RNA sequencing showed that piRNA biogenesis and ping-pong amplification remain largely intact. Together, these datasets identify MORC2A as a male germline chromatin regulator required for epigenetic silencing of young transposable elements.
• TREX1 limits anti-tumor immunity by degrading short cytosolic DNA molecules
  GSE334899Mus musculus4 个样本2026-10-31

  TREX1 has recently emerged as a promising therapeutic target in cancer owing to its role in degrading cytosolic DNA and suppressing type I interferon signaling. However, the nature of the immunostimulatory DNA species degraded by TREX1 remains elusive. Here, we show that TREX1 deficiency in murine lung and melanoma tumor cells leads to a substantial, MRE11-dependent increase in short cytosolic DNA fragments that originate preferentially from transcriptionally active regions of the genome, without a corresponding increase in micronuclei. These fragments robustly activate interferon-stimulated genes and drive differentiation of pro-inflammatory macrophages. In syngeneic mice, tumors derived from Trex1-knockout cells exhibit delayed growth, increased sensitivity to anti-PD-1 immune checkpoint blockade, and extended survival. These effects depend on an intact immune system and foster durable anti-tumor memory. Together, our results reveal that short, transcription-derived cytosolic DNA fragments are key TREX1 substrates mediating immune activation in cancer, establishing TREX1 inhibition as a compelling strategy to enhance tumor immunogenicity.
• Transcriptomic characterization of macrophage subtype and behavior in early stage myocardial infarction
  GSE333790Mus musculus9 个样本2026-10-31

  Elucidate the spatiotemporal behavior of specific macrophage subtypes during AMI and identify novel genes with prospective therapeutic potential.
• EZH2 inactivation drives MAPK-dependent vulnerability to MEK inhibition in RAS-mutant CMML
  GSE333450Mus musculus7 个样本2026-10-31

  Chronic myelomonocytic leukemia (CMML) is a heterogeneous hematologic malignancy with limited therapeutic options. Although RAS and RAS-modifying mutations (RASmut) are common and associated with poor prognosis, targeting RAS signaling has shown limited clinical success. Here, we define co-occurrence of RASmut and EZH2 inactivation (EZH2inact) as a distinct molecular subgroup of CMML characterized by aggressive disease biology. Mechanistically, RASmutEZH2inact drives selective MAPK/ERK hyperactivation in mature myeloid cells and hematopoietic stem and progenitor compartments. Transcriptomic analysis of a large independent myeloid neoplasm cohort (Beat-AML) further supports this finding, demonstrating selective activation of gene signatures of MAPK/ERK activation in RASmutEZH2inact cases. Functionally, this signaling activation promotes proliferation and myelomonocytic differentiation in human and murine models. Therapeutically, this MAPK/ERK upregulation confers increased sensitivity to MEK inhibition (MEKi). In a murine RasmutEzh2inact-driven CMML model, MEKi suppresses MAPK/ERK activity and reduces leukemic burden by impairing proliferation and myelomonocytic differentiation without inducing cell death. In primary human CMML samples ex vivo, MEKi shows stronger anti-proliferative effects in RASmutEZH2inact specimens compared with RASmut samples. Drug-sensitivity data from the Beat-AML cohort further supported this. Ultimately, these findings were confirmed in a patient-derived xenograft model, where MEKi reduced the leukemic burden by selectively inhibiting the proliferation of transplanted human RASmutEZH2inact leukemic cells. In summary, our data define RASmutEZH2inact CMML as a clinically relevant subgroup with selective MAPK/ERK hyperactivation and increased sensitivity to MEKi. They provide a mechanistic explanation for the limited efficacy of MEK inhibitors in unselected CMML and support molecularly guided use of MEK-targeted therapy in this patient population.
• Single cell transcriptomic sequencing in common mouse models of atherosclerosis
  GSE332811Mus musculus8 个样本2026-10-31

  A single cell analysis of mice aorta to perform comprehensive comparison among common mouse models of atherosclerosis

  单细胞
• Stereo-seq of aortic atherosclerotic lesions in common mouse models
  GSE331239Mus musculus3 个样本2026-10-31

  A spatial transcriptomic analysis of aortic root atherosclerotic lesions for a comparison between common mouse models of atherosclerosis

  空间转录组
• Exposure to perfluorooctanoic acid perturbs serotonin signaling in maternal pancreatic islets and induces gestational diabetes in mice
  GSE330582Mus musculus8 个样本2026-10-31

  [working abstract for manuscript, in style of how is required for EHP] Background: Perfluorooctanoic acid (PFOA) has been linked to gestational diabetes and other adverse pregnancy outcomes in humans. Despite the association, the mechanisms by which PFOA contributes to GDM have not been studied. The present study investigated whether PFOA exposure resulted in lower pancreatic islet serotonin abundance and β-cell proliferation, glucose intolerance, impaired insulin secretion, insulin resistance, and robust transcriptional changes underlying pancreatic islet adaptation, which provided evidence for a mechanism of PFOA-induced GDM. Objectives: The purpose of this study was to assess whether PFOA exposure impairs pancreatic islet serotonin-driven β-cell proliferation and causes GDM in a C57BL/6J mouse model. Methods: Analysis of pancreatic islet serotonin abundance and β-cell proliferation were measured by immunofluorescence. Metabolic assays, including glucose tolerance test, glucose-stimulated insulin secretion, and insulin tolerance test were used to characterize GDM phenotypes. Bulk RNA sequencing was used to analyze differentially expressed genes and gene set enrichment in pancreatic islets isolated from control and PFOA-exposed mice. Results: PFOA exposure lowered islet serotonin abundance and β-cell proliferation in gestational day (GD) 12.5 pregnant dams. PFOA exposure was associated with glucose intolerance, impaired insulin secretion, and insulin resistance in GD16.5 pregnant dams. β-cell proliferation at GD12.5 and glucose tolerance at GD16.5 was improved in PFOA-exposed dams treated with a serotonin receptor 2B agonist (BW-732C86). RNAseq uncovered four differentially expressed genes and a broad reduction in coordinated transcriptional pathway activity in maternal pancreatic islets of PFOA-exposed GD12.5 dams. Discussion: PFOA-induced glucose intolerance was associated with perturbed pancreatic islet serotonin abundance.

  扰动筛选
• Single-cell atlas reveals shared early microenvironmental remodeling in colorectal polypogenesis
  GSE327909Homo sapiens6 个样本2026-10-31

  Colorectal polyps are the earliest precancerous lesions in colorectal carcinogenesis, but their common microenvironmental drivers remain incompletely defined. We performed single-cell RNA sequencing on paired normal mucosal and colorectal polyp tissues from 3 patients with unselected lesions, including hyperplastic polyps and tubular adenomas. After quality control, 31,147 high-quality cells were obtained. Comparative analysis revealed four conserved hallmarks of colorectal polyps relative to normal mucosa: disrupted epithelial homeostasis characterized by stem cell expansion, Paneth cell reduction, and Wnt pathway activation; pro-inflammatory polarization of CD4+ T cells with increased Th17 cells and activation of NF-kB/IL-17-related pathways; functional reprogramming of CD8+ T cell subsets, especially decreased IELs with specialized immune functions; and extensive remodeling of immune-epithelial intercellular communication, including CD55-ADGRE5, MIF-CD74, and GZMA-PARD3 signaling axes. These data provide a single-cell atlas of shared microenvironmental changes in early colorectal polypogenesis.

  单细胞细胞图谱
• 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
• 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.
• 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
• 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.
• 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.
• 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 [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.
• 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.
• Geometric inference of cross-species transcriptome correspondence [scRNA-Seq]
  GSE307645Macaca fascicularis; Pan troglodytes; Gorilla gorilla; Pongo abelii; Homo sapiens; Mus musculus6 个样本2026-10-31

  Sequence homology underpins cross-species analysis but cannot identify evolutionarily distinct genes that play analogous regulatory roles. Furthermore, ethical restrictions on human experiments necessitate analytical frameworks that translate insights from other animals to humans. To address these challenges, we develop Species-OT, a cross-species transcriptome analysis framework based on Gromov-Wasserstein optimal transport, which quantitatively compares the geometry of transcriptome distributions. Given a pair of bulk or single-cell RNA-sequencing datasets, Species-OT returns a gene-to-gene correspondence capturing probabilistic alignments of regulatory roles, and a transcriptomic distance quantifying overall divergence. Applied pair wise, Species-OT yields a transcriptomic discrepancy array and a hierarchical clustering tree analogous to a phylogenetic tree. We validate Species-OT using bulk RNA-seq data from human, mouse, and macaque germ cell specification as well as scRNA-seq data from pluripotent stem cells of six mammalian species. Species-OT identifies evolutionarily related and distinct gene correspondences including biologically unexplored candidates, while transcriptomic discrepancies recapitulate expected species relationships.

  单细胞
• Deciphering the diversities of CTCF and CTCF-s in human embryonic stem cells
  GSE280503Homo sapiens6 个样本2026-10-31

  In this study, transient transcriptome sequencing (TT-seq) was performed to dectect the impact of the overexpression of CTCF-s on nascent RNA and antisense RNA.