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最新 10月31日

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  • 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
  • HFpEF HMDP: ventricular RNA-seq in an expanded BXD strain panel
    GSE348752Mus musculus194 个样本2026-10-30

    Systems genetics strategy across multiple Hybrid Mouse Diversity Panel (HMDP) cohorts. RNA sequencing of ventricles from HFpEF mice was performed primarily in an expanded panel of BXD strains, together with a small number of classic inbred strains. This submission represents the expanded BXD component of the HFpEF HMDP project.

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

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

  • Acute Degradation of Pumilio Proteins Reveals a Biphasic Posttranscriptional Regulatory Hierarchy in Embryonic Stem Cell Fate Decision [RNA-Seq]
    GSE310694Mus musculus84 个样本2026-10-30

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

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

    This study examines time-dependent hepatic responses to 4,4'-methylenedianiline (MDA), a cholestatic hepatotoxicant, administered to male C57BL/6JJcl mice in drinking water. Liver RNA sequencing was performed in separate terminal cohorts sampled on Days 1, 2, 3, 4, and 8 after exposure to control tap water, thioacetamide (TAA; 300 mg/L), or MDA (750 mg/L). The dataset comprises 72 poly(A)-selected liver RNA-seq libraries and provides gene-level expression measurements for characterizing temporal transcriptional changes and comparing the MDA model with the TAA reference condition.

  • Bulk RNA-seq atlas of cytokine-polarized murinebone-marrow-derived macrophages (BMDMs) across inflammatory, regulatory, and reparative stimuli
    GSE315641Mus musculus81 个样本2026-10-28

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

    扰动筛选细胞图谱
  • Micropatterning for soma, proximal neurite, and distal neurite RNA profiling
    GSE352013Mus musculus59 个样本2026-10-26

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

  • RNA Polymerase II Dynamics in Antiviral NK Cell Responses
    GSE351578Mus musculus68 个样本2026-10-26

    This SuperSeries is composed of the SubSeries listed below.

    SuperSeries
  • The nail mesenchyme creates a regeneration-specific ligand environment that orchestrates mammalian regeneration versus fibrotic wound healing
    GSE326776Mus musculus98 个样本2026-10-26

    The adult digit tip is one of the few privileged mammalian tissues that can regenerate. Here, we have asked why this is so. We show, using single cell spatial transcriptomics and genetic mouse models that regeneration requires the nail organ and associated inductive nail mesenchyme, and that in their absence the digit tip undergoes fibrotic wound-healing. We further show the nail organ/mesenchyme orchestrates a highly-organized regenerative response where mesenchymal cells are reprogrammed to a blastema state and re-epithelialization is enhanced. It does this by creating a regeneration-specific ligand environment that is absent in the nonregenerative condition and that includes multiple BMPs. Loss of downstream BMP signaling by genetic deletion of Smad4 in all mesenchymal cells or specifically in the nail mesenchyme inhibits multiple aspects of the regenerative response, including expression of regeneration-specific ligands. Thus, the nail mesenchyme creates a BMP-rich local ligand environment that reprograms mesenchymal cells to a blastema state and promotes tissue regeneration versus fibrotic wound-healing, findings with implications for tissue repair and anti-fibrosis strategies.

    单细胞空间转录组