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
• Paternal methylphenidate exposure alters sperm miRNAs and induces intergenerational behavioral and transcriptional changes that are largely reversed by washout
  GSE341541Mus musculus12 个样本2026-10-31

  To determine whether paternal methylphenidate exposure alters sperm small noncoding RNA profiles and whether these changes are reversible after drug withdrawal, male BALB/c mice were administered methylphenidate (15 mg/kg) or saline (10 mL/kg) for 28 days. Cauda epididymal sperm were collected immediately after treatment or after a 40-day washout period and analyzed by small RNA sequencing.
• 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.
• NLRP3 inflammasome-mediated pyroptosis exacerbates insulin resistance upon exposure to nanoplastics with different surface chemistries
  GSE338308Danio rerio15 个样本2026-10-31

  The surface chemical properties of nanoplastics (NPs), such as surface charge and functional groups, can markedly influence their toxicological effects. Recent studies have shown that NPs can disrupt glucose homeostasis. However, under metabolically susceptible conditions, such as hyperglycemia and metabolic dysfunction, differences in metabolic toxicity and the underlying mechanisms among surface-modified NPs remain unclea
• Targeting ERO1α Triggers Tumor Immunosurveillance in Triple-Negative Breast Cancer
  GSE337796Mus musculus24 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Targeting ERO1α Triggers Tumor Immunosurveillance in Triple-Negative Breast Cancer [RNA-seq]
  GSE337795Mus musculus12 个样本2026-10-31

  Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited responsiveness to immune checkpoint blockade. Here, we identify endoplasmic reticulum oxidoreductase 1 alpha, a key regulator of oxidative protein folding, as a determinant of tumor immunogenicity and immunotherapy response in TNBC. Unbiased proteomic profiling demonstrated that ERO1α deficiency remodels the TNBC glycoproteome, leading to enrichment of pathways associated with innate immune signaling. Although ERO1α loss did not affect tumor cell growth, it reshaped the immune tumor microenvironment, enhancing antigen presentation, altering myeloid-cell composition, and modulating PD-1/PD-L1–associated signaling. Functionally, ERO1α deficiency sensitized otherwise refractory TNBC tumors to PD-1 blockade, resulting in durable tumor regression in immunocompetent hosts. In contrast, ERO1α deletion in bone marrow–derived immune cells had minimal effects on tumor growth or therapeutic response, supporting an ERO1α tumor-intrinsic mechanism. Pharmacologic inhibition of ERO1α with the novel small-molecule inhibitor I29 phenocopied ERO1α genetic deletion and enhanced the efficacy of anti–PD-1 therapy. Together, these findings identify ERO1α-dependent glycoproteome remodeling as a regulator of antitumor immunity and a therapeutically actionable mechanism of immune checkpoint responsiveness in TNBC.
• Targeting ERO1α Triggers Tumor Immunosurveillance in Triple-Negative Breast Cancer [scRNA-seq]
  GSE336881Mus musculus12 个样本2026-10-31

  Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited responsiveness to immune checkpoint blockade. Here, we identify endoplasmic reticulum oxidoreductase 1 alpha, a key regulator of oxidative protein folding, as a determinant of tumor immunogenicity and immunotherapy response in TNBC. Unbiased proteomic profiling demonstrated that ERO1α deficiency remodels the TNBC glycoproteome, leading to enrichment of pathways associated with innate immune signaling. Although ERO1α loss did not affect tumor cell growth, it reshaped the immune tumor microenvironment, enhancing antigen presentation, altering myeloid-cell composition, and modulating PD-1/PD-L1–associated signaling. Functionally, ERO1α deficiency sensitized otherwise refractory TNBC tumors to PD-1 blockade, resulting in durable tumor regression in immunocompetent hosts. In contrast, ERO1α deletion in bone marrow–derived immune cells had minimal effects on tumor growth or therapeutic response, supporting an ERO1α tumor-intrinsic mechanism. Pharmacologic inhibition of ERO1α with the novel small-molecule inhibitor I29 phenocopied ERO1α genetic deletion and enhanced the efficacy of anti–PD-1 therapy. Together, these findings identify ERO1α-dependent glycoproteome remodeling as a regulator of antitumor immunity and a therapeutically actionable mechanism of immune checkpoint responsiveness in TNBC.

  单细胞
• MicroRNA annotations from the parasitic plant Cuscuta saururi
  GSE335728Cuscuta saururi14 个样本2026-10-31

  The Cuscuta genus of parasitic plants is widespread and can impact agricultural productivity. Previous studies of C. campestris have described the existence of a special type of microRNA that functions to enter host tissues and regulate host mRNAs. These "interface-induced" microRNAs are uniquely transcribed by RNA polymerase III, have a common promoter element, and specifically accumulate in haustorial tissues of the parasite. Here, we investigate the existence of such "interface-induced" microRNAs in a second Cuscuta species, C. saururi. C. saururi is a recently resurrected species that forms part of the C. gronovii species complex. We used a highly contiguous genome assembly of C. saururi, along with small RNA-seq, to annotate both the interface-induced and canonical microRNA genes of C. saururi.
• MORC2A is required for DNA methylation and H3K9me3 at retrotransposons in the male germline
  GSE335170Mus musculus29 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• 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 [RNA-seq]
  GSE335166Mus musculus10 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.
• Sarm1 Gates the Transition from Protective to Repair Schwann Cell States Following Nerve Injury [snRNA-Seq]
  GSE332913Mus musculus11 个样本2026-10-31

  Schwann cells (SCs) transition into a Repair state after peripheral nerve injury; however, the early SC injury response preceding this transition remains poorly understood. We demonstrate that Sarm1, a key regulator of axon degeneration, is expressed and upregulated in SCs after nerve injury. Cell-type-specific Sarm1 knockout SCs exhibit enhanced axon protection in vitro, and SC- and glia-specific Sarm1 deletion confers axon protection in mouse sciatic nerve and Drosophila wing injury models. Single-nucleus RNA sequencing revealed that Sarm1-deficient SCs are enriched in a distinct cluster expressing genes with developmental roles in axon and myelin protection, with increased oxidative phosphorylation gene expression across all injured SC states. We propose that Sarm1 gates the transition from a Protection-Associated Schwann Cell (PASC) state to a Repair SC state, establishing Sarm1 as a multi-functional regulator with implications for peripheral neuropathies and neurodegenerative diseases.

  单细胞
• Sarm1 Gates the Transition from Protective to Repair Schwann Cell States Following Nerve Injury [RNA-seq]
  GSE332854Mus musculus12 个样本2026-10-31

  Schwann cells (SCs) transition into a Repair state after peripheral nerve injury; however, the early SC injury response preceding this transition remains poorly understood. We demonstrate that Sarm1, a key regulator of axon degeneration, is expressed and upregulated in SCs after nerve injury. Cell-type-specific Sarm1 knockout SCs exhibit enhanced axon protection in vitro, and SC- and glia-specific Sarm1 deletion confers axon protection in mouse sciatic nerve and Drosophila wing injury models. Single-nucleus RNA sequencing revealed that Sarm1-deficient SCs are enriched in a distinct cluster expressing genes with developmental roles in axon and myelin protection, with increased oxidative phosphorylation gene expression across all injured SC states. We propose that Sarm1 gates the transition from a Protection-Associated Schwann Cell (PASC) state to a Repair SC state, establishing Sarm1 as a multi-functional regulator with implications for peripheral neuropathies and neurodegenerative diseases.

  单细胞
• 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
• Single-cell analysis reveals transcriptomic patterns in active macrophage activation syndrome and therapeutic potential of albumin-fused interleukin-10 in a mouse model
  GSE331089Homo sapiens20 个样本2026-10-31

  Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperinflammatory conditions characterized by excessive immune activation and cytokine production. To clarify immune cell characteristics and identify potential therapeutic targets in MAS, we performed single-cell RNA sequencing (scRNA-seq) on bone marrow and peripheral blood samples from patients with newly developed MAS caused by diverse etiologies. To broaden the current knowledge of the immune landscape in the bone marrow, we performed scRNA-Seq of bone marrow cells and isolated blood leukocytes obtained from MAS patients using the Seq-Well.

  单细胞
• 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
• 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
• MUC13 enhances IL-17 signaling pathway activity in nasal epithelial cells
  GSE329876Homo sapiens12 个样本2026-10-31

  MUC13 is a membrane-bound mucin involved in epithelial protection and barrier maintenance, but its role in nasal epithelial inflammation remains unclear. This study aimed to investigate the function of MUC13 in nasal epithelial cells (NECs) and its potential involvement in inflammatory signaling. Primary NECs were isolated from patient-derived inferior turbinate mucosa, and MUC13 overexpression was established by direct transfection of human MUC13 mRNA. RNA sequencing and bioinformatics analyses were performed to characterize transcriptomic changes.
• GPR124 upregulation protects AML blasts from lipotoxicity
  GSE329506Mus musculus12 个样本2026-10-31

  GPR124 (ADGRA2), a member of the Adhesion G Protein-Coupled Receptor family, has an established role in the embryonic development of the central nervous system vasculature. However, its function in the context of acute myeloid leukemia (AML) remains unexplored. Transcriptome studies revealed upregulation of GPR124 in AML CD34+ blasts compared to healthy counterparts. Lentiviral overexpression of an GPR124-EGFP fusion protein indicated both plasma membrane and intracellular localization. Immunoprecipitation followed by LC-MS/MS showed strong enrichment of intracellular proteins associated with vesicles and vesicle transport, focal adhesion, actin cytoskeleton, and lipid droplets (LDs). In murine bone marrow mesenchymal stromal cells stimulated towards adipocytic differentiation, CRISPR-Cas9 mediated knockout of Gpr124 (Gpr124KO) reduced LD size, while total neutral lipid accumulation showed an increasing trend. In AML cells, lipidomic studies revealed increased baseline triacylglycerol (TG) levels in GPR124KO cells, suggesting altered LD metabolism. Since TGs are key components of LDs and its accumulation is a known response to lipid peroxidation, we next assessed ferroptosis sensitivity. Indeed, GPR124KO cells were significantly more sensitive to ferroptosis induction by GPX4 inhibition, accompanied by increased reactive oxygen species (ROS) and accumulation of lipid peroxidation. Additionally, GPR124KO cells were more sensitive to DGAT1 inhibition, a key enzyme in LD formation, and combination with the ferroptosis inducer RSL3 was synergistic in GPR124KO cells. Together, our findings indicate that GPR124 is essential for maintaining stable lipid homeostasis in AML and identify GPR124 and LD metabolism as potential therapeutic targets for inducing ferroptosis-mediated cell death.
• 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