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。

• Transmural Single-Nucleus Transcriptomics Nominates Candidate Disease Programs in Human Necrotizing Enterocolitis
  GSE351352Homo sapiens10 个样本2026-10-26

  Necrotizing enterocolitis (NEC) is a life-threatening disease of premature infants marked by inflammation, ischemia, mucosal injury, and, in advanced cases, necrosis extending into deeper layers of the intestinal wall. Because NEC affects specialized, interacting cells in a developing intestine, we used single-nucleus transcriptomics to build a transmural, cell-type-resolved map and nominate hypothesis-generating disease programs distinct from maturation. Full-thickness intestinal specimens from fetal/prenatal controls, acute NEC cases, and infant controls were analyzed by single-nucleus RNA sequencing (snRNA-seq). Fetal and infant samples served as developmental references. Analyses included cell annotation, NEC-versus-infant differential expression, gene ontology (GO), cross-lineage recurrence, cell-death signatures, and developmental maturity. We profiled 53,735 nuclei by snRNA-seq and resolved 34 epithelial, stromal, vascular, immune, neuronal, glial, and smooth-muscle populations. We used a morphology-based nuclei scoring system for sample selection that predicted high-quality transcript recovery. NEC nuclei were represented across this cellular landscape, with recurrent gene-expression changes suggesting shared inflammatory recruitment, antimicrobial/redox defense, stress adaptation, complement/vascular activation, reduced homeostatic signaling, and cell-death-associated regulation. Developmental maturity analysis identified fetal-like expression levels in subsets of NEC-regulated genes. Proliferative crypt populations retained DNA-repair/cell-cycle programs with inflammatory, hypoxic, and ER-stress features, while absorptive enterocytes showed reduced digestive, transport, detoxification, and terminal villus-function programs. Secretory-lineage changes implicated goblet mucus-barrier responses with reduced glycosylation, trafficking, and hydration; enteroendocrine changes in epithelial defense, metabolic stress, and neural signaling; and Paneth cell retention of antimicrobial effector transcripts despite altered ER quality control, autophagy, and granule delivery in NEC. Non-epithelial programs implicated stromal Wnt/BMP niche loss, impaired lymphatic drainage/scavenging, macrophage cytokine activation with reduced clearance machinery, neuroglial circuit defects, and altered smooth-muscle contraction-relaxation balance. This single nuclear intestinal cell atlas nominates multicellular programs that may govern NEC initiation, progression toward tissue destruction, and resolution toward functional recovery.

  单细胞细胞图谱
• TNFR2 agonism increases tissue and effector Treg cells
  GSE344965Mus musculus12 个样本2026-10-26

  Autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus are driven by chronic inflammation and tissue damage. Regulatory T (Treg) cells are critical for maintaining immune tolerance, yet their therapeutic use is limited by stability and tissue homing. Here, we demonstrate that agonism of tumor necrosis factor receptor 2 (TNFR2) increases effector and tissue-competent Treg cell progenitors in mice and humans. Single-cell RNA sequencing reveals that TNFR2 is highly expressed on early and late non-lymphoid tissue Treg cell precursors, with expression strongly correlated with the BATF-driven tissue Treg cell transcriptional program. In vivo, a single dose of TNFR2 agonist promotes the clonal commitment of Treg cells to effector and tissue lineage, increasing tissue Treg cell populations in lymphoid and peripheral tissues. This increase is associated with enhanced suppressive function, epigenetic stability (preserved FOXP3 CNS2 demethylation), and resistance to inflammatory conversion. In murine models of skin inflammation and experimental autoimmune encephalomyelitis, TNFR2 agonism ameliorates disease severity in a dose-dependent manner. Critically, in human Treg cells, TNFR2 agonism induces elements of the tissue residency transcriptional program—including upregulation of LAYN, CCR8, CCR4 and TIGIT—while maintaining lineage stability. These findings establish TNFR2 signaling as a central driver of effector and tissue Treg cell differentiation and position TNFR2 agonism as a transformative strategy for generating stable, tissue-competent effector Treg cells as a promising immunomodulatory therapy for autoimmune and inflammatory diseases.

  单细胞
• Recordanelles for transcriptome-wide single-cell RNA recording in human cells [dataset_2 RNA-Seq]
  GSE344934Homo sapiens48 个样本2026-10-26

  Transcriptomic measurement technologies provide powerful approaches to understand biology but are limited to providing either a high-resolution snapshot at a moment in time or a low-resolution history of transcription constrained to a few genes over a narrow time range. Here, we introduce the “recordanelle”, a single-component synthetic organelle capable of recording the transcriptome in human cells. Recordanelles are composed of a mitochondrial membrane anchor, a condensate assembler and a poly-A-binding protein. We demonstrate that the recordanelle can be engineered to recruit engineered RNAs or a sampling of up to 90% of all endogenous mRNAs and protect them over several days. We further show that transient and dynamic transcriptional responses resulting from inducible promoters or interferon signaling are preserved throughout time within the recordanelle at the single-cell level. This work provides a non-disruptive and unbiased transcriptome-wide single-cell RNA recording technology to enable a deeper understanding of biology.

  单细胞
• Effect of TNFR2 agonism on CD4+ T cells (single-cell level) from healthy and SLE donors
  GSE344526Homo sapiens35 个样本2026-10-26

  We treated peripheral blood mononuclear cells from healthy donors and systemic lupus erythematosus (SLE) patients with (i) a human-specific tetravalent VHH-Fc fusion TNFR2 agonist, (ii) isotope control VHH and (iii) an IL2-mutein.

  单细胞
• Attenuation of DOK3 re-programs tumor-associated macrophages to enhance anti-PD-1-mediated cancer immunotherapy [scRNA-seq MC38]
  GSE341712Mus musculus12 个样本2026-10-26

  Downstream of Kinase 3 (DOK3) is an adaptor protein that binds and modulates Caspase recruitment domain-containing protein 9 (CARD9) signaling but the role for DOK3 during tumor immune escape remains unclear. Here, we revealed immunosuppressive Osteopontin (SPP1+) tumor-associated macrophages (TAMs) to highly express DOK3 while DOK3low/neg TAMs express CARD9 and T cell-homing chemokines within the tumor microenvironment (TME). Interestingly, Dok3-/- mice showed decreased tumor growth and improved response to anti-PD-1 therapy. While DOK3 is constitutively expressed by macrophages, blocking its interaction with CARD9 enhances JNK signaling to reprogram TAMs for improved homing and activation of T cells. Further spatial studies clarified the localization of DOK3high TAMs within the TME and an association of DOK3 expression with progressive disease in an ongoing Phase II study of Lenvatinib/Pembrolizumab in recurrent clear cell gynecological carcinomas. Overall, targeting DOK3-CARD9 axis may represent a new avenue to overcome resistance in cancer immunotherapy by driving the emergence of favorable response-associated TAM states.

  单细胞空间转录组