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。

• 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
• Hyperglycemia drives an activated, lipid-laden non-classical monocyte phenotype in diabetes
  GSE339503Mus musculus36 个样本2026-10-26

  The presence of lipid-loaded macrophages in the artery wall and kidney characterizes diabetic atherosclerotic cardiovascular disease and diabetic kidney disease, respectively. Monocytes, the bone marrow-derived precursors of macrophages, accumulate lipids in response to hypercholesterolemia; however, whether diabetes directly alters monocyte lipid loading remains unclear. Using unbiased proteomics, we show that diabetes profoundly affects circulating monocytes, leading to upregulation of glucose metabolism pathways and suppression of cholesterol homeostasis pathways, indicative of lipid loading, particularly in non-classical monocytes. Functional analyses confirmed that non-classical monocytes exhibit increased glucose uptake and a lipid-loaded phenotype in three distinct mouse models of diabetes, and that they are also more lipid-loaded in people living with diabetes. The increased lipid loading of non-classical monocytes was not only due to dyslipidemia but to elevated glucose levels. Finally, we find that non-classical monocytes traffic to the kidney and contribute to a foamy population of kidney macrophages in a mouse model of diabetes. Together, these findings suggest that hyperglycemia in diabetes drives the reprogramming of non-classical monocytes, leading to lipid loading and the accumulation of lipid-loaded macrophages in the kidney.
• Effect of TNFR2 agonism on human regulatory T cells
  GSE339300Homo sapiens10 个样本2026-10-26

  We isolated CD45RA+ Treg cells from human peripheral blood and treated them in vitro using a human TNFR2 agonist or a control VHH.
• Endonucleolytic mRNA decay associated with damaged tRNAs occupying the ribosome
  GSE334514Saccharomyces cerevisiae45 个样本2026-10-26

  Aberrant events during mRNA translation trigger ribosome-dependent quality control mechanisms that tune mRNA decay and gene expression. Here, we describe endonucleolytic mRNA decay associated with damaged tRNAs at the ribosome. We provide evidence that this process is associated with a nicked tRNA that our data place in the ribosomal A-site, where it contributes to ribosome stalling. Genetic analyses suggest that the pathway is independent of canonical mRNA decay machinery, and we identify the CTDK-I complex as a critical regulator. These findings suggest that the ribosomal A-site can engage damaged tRNAs and that this engagement can trigger mRNA decay, broadening our understanding of translation elongation and tRNA biology.
• Preconception Paternal PFAS Exposure Reprograms the Placental Epigenome
  GSE333805Mus musculus28 个样本2026-10-26

  The placenta plays a vital role in supporting fetal growth and development by facilitating nutrient exchange, hormone signalling and immune regulation. Environmental toxicants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) can disrupt placental homeostasis, leading to increased risk of disease later in life. Paternal environmental exposures may influence offspring health by inducing epigenetic changes in sperm, which may affect sex-dependent placental programming. Here, male mice were exposed to a PFAS mixture (PFOS, PFOA, PFNA, PFHxS, GenX; 20 μg/L each) for 10 weeks and mated with unexposed females. We identified 6,656 and 3,242 differentially methylated regions (DMRs) in E12.5 placentas of female and male offspring, respectively. Female placentas showed predominantly hypermethylation (78.5%), whereas male placentas were mostly hypomethylated (62%). Gene ontology analyses linked female placental DMRs to cell and embryonic morphogenesis, and male DMRs to anatomical size regulation and hemostasis. Bulk RNA sequencing revealed 168 and 148 differentially expressed genes (DEGs) in female and male placentas, respectively. Female DEGs were related to immune regulation, while male DEGs were involved in muscle and mesenchyme development. Sex-by-PFAS interaction models identified distinct methylation and transcription biological pathways. Overlap analysis between F0 sperm and F1 placentas identified 265 shared genes, including 289 female-specific and 124 male-specific genes. Paternal exposure to the PFAS mixture increased glycogen concentrations in male, but not female, placentas. No effects were observed at imprinted loci. These findings demonstrate that paternal preconception exposure to a PFAS mixture alter placental epigenomic and transcriptomic landscapes, which may contribute to sex-dependent trajectories of fetal health and development and offspring phenotypes.
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses [Histone ChIP-Seq]
  GSE326752Mus musculus26 个样本2026-10-26

  Natural killer (NK) cells are innate lymphocytes that uniquely exhibit both innate and adaptive responses towards certain pathogens. During cytomegalovirus (CMV) infection, antigen-specific NK cells will generate a long-lived pool of memory cells with enhanced responses to secondary infection. The underlying molecular mechanisms that regulate early innate effector functions and delayed adaptive proliferation followed by longevity during antiviral NK cell differentiation remain to be fully understood. Here, we investigated the dynamics of serine-5 phosphorylated RNA Polymerase II (Pol IIS5P) occupancy in NK cells ex vivo during mouse CMV (MCMV) infection. During the initial NK cell antiviral response, Pol IIS5P occupancy increased broadly across the genome, at both upregulated and downregulated genes relative to NK cells at rest. NK cells across response states showed distinct enrichment of Pol IIS5P at transcriptional start sites (TSS) versus non-promoter regions with select genes maintaining Pol IIS5P occupancy throughout MCMV infection to the memory phase. Thus, our findings illustrate the dynamic Pol IIS5P genomic occupancy in NK cells during antiviral immunity.
• MEK2 Suppresses IL-4 Polarization via PPARγ and Negatively Impacts Macrophage Epithelial Crosstalk to Delay Repair
  GSE326260Mus musculus12 个样本2026-10-26

  In this study, we tested our hypothesis that MEK2 impairs IL-4 (reparative) macrophage function. Transcriptional profiling of WT and Mek2-/- bone marrow derived macrophages (BMDM) revealed that MEK2 inhibits a subset of IL-4-dependent gene expression, including genes enriched in wound repair pathways.
• Overlapping MHC class I/II epitopes program monocyte-derived dendritic cells toward a cDC1-like state via mTORC1 pathway inhibition [ChIP-Seq]
  GSE324817Mus musculus12 个样本2026-10-26

  Viral infection polarizes monocyte derived dendritic cells (moDC) to initiate type 1 immune responses. The availability of homologous (overlapping) MHC class I and II epitopes, an occurrence associated with viral infection, significantly enhances this process; however, the underlying mechanism(s) remain unclear. We demonstrate that moDC loaded with homologous MHC epitopes acquire a cDC1-like phenotype in a process governed by mTORC1. mTORC1 pathway inhibition among cDC1-like cells leads to NF-kB-mediated expression of IL-12 and other type I immune polarizing genes. The cDC1-like signature was also significantly enhanced in clinical moDC vaccine products for glioblastoma and PDAC made through methodologies that enforced class I and II antigenic homology. Collectively, these findings reveal a novel mechanism of immune governance that may also be exploited in cancer immunotherapy.
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses [Pol IIS5P CUT&RUN]
  GSE318335Mus musculus22 个样本2026-10-26

  Natural killer (NK) cells are innate lymphocytes that uniquely exhibit both innate and adaptive responses towards certain pathogens. During cytomegalovirus (CMV) infection, antigen-specific NK cells will generate a long-lived pool of memory cells with enhanced responses to secondary infection. The underlying molecular mechanisms that regulate early innate effector functions and delayed adaptive proliferation followed by longevity during antiviral NK cell differentiation remain to be fully understood. Here, we investigated the dynamics of serine-5 phosphorylated RNA Polymerase II (Pol IIS5P) occupancy in NK cells ex vivo during mouse CMV (MCMV) infection. During the initial NK cell antiviral response, Pol IIS5P occupancy increased broadly across the genome, at both upregulated and downregulated genes relative to NK cells at rest. NK cells across response states showed distinct enrichment of Pol IIS5P at transcriptional start sites (TSS) versus non-promoter regions with select genes maintaining Pol IIS5P occupancy throughout MCMV infection to the memory phase. Thus, our findings illustrate the dynamic Pol IIS5P genomic occupancy in NK cells during antiviral immunity.
• Spatially Decoding Interactypes of Vascular and Synaptic Remodeling in the Glioblastoma Tumor Microenvironment by Surprisal Information-Theoretic Analysis
  GSE317289Homo sapiens10 个样本2026-10-26

  Glioblastoma (GBM) is a highly heterogeneous and invasive brain cancer, where interactions between tumor cells, vasculature, and neurons shape disease progression and therapeutic resistance. To better understand the spatial organization of these processes, we profiled ten tumor samples from five patients, one sample from T1-constrast-enhanced and one from non-contrast enhanced regions using spatial transcriptomic sequencing and multiplexed protein imaging. While each patient’s tumor presents a unique landscape, together these samples capture all major histological and spatial niches of GBM, enabling a complete picture of the tumor microenvironment and cell–cell “interactypes.” By applying surprisal analysis, an information-theoretic framework, for the first time to spatial omics data, we decomposed gene expression into orthogonal constraint modes that uncovered distinct processes such as extracellular matrix remodeling, vascular-associated invasion, and neuron–tumor synaptic interactions, each with well-defined molecular mechanism. Complementing this approach, a spatial ligand–receptor interactype analysis mapped specific communication events across niches. Within the perivascular niche, we observed collagen–integrin signaling linked to a trajectory from astrocyte-like to mesenchymal-like tumor states. At neuron–tumor interfaces, synaptic remodeling emerged, characterized by NLGN1–NRXN1 and SEMA5A–MET interactions together with enrichment of neuronal gene modules including MAP2 and CALM1. These findings suggest that surprisal analysis can reveal vascular remodeling and neuron-tumor crosstalk are critical mechanisms of GBM progression. This study demonstrates the use of surprisal information-theoretic analysis of spatial omics data to expose hidden spatial programs with mechanistic insights and the interactype mapping to decode the GBM biology across all major tumor niches, pointing toward the discovery of potential therapeutic vulnerabilities mediated by cell-cell interaction and microenvironments.

  空间转录组
• Placental insufficiency causes fetal growth restriction in mice lacking Delta-like homologue 1
  GSE313753Mus musculus31 个样本2026-10-26

  Fetal growth restriction (FGR) affects between 3-7% of pregnancies, is associated with increased perinatal morbidity and mortality, and linked to failure of placental function. The placenta is the key transient organ in pregnancy that makes direct contact with the maternal circulation and directs nutrient transfer, intermediary metabolism and the production of hormones that drive maternal metabolic adaptations essential for pregnancy and lactation. The exchange surface of the placenta is formed in early development by the interaction between trophoblast cells that enclose the maternal blood and extraembryonic mesodermal cells that comprise the fetal vasculature. Despite recent insights into trophoblast development derived from novel in-vitro approaches, the processes driving extraembryonic mesoderm development are not well explored. This is due to a dearth of studies employing unbiased approaches to interrogate extraembryonic mesoderm cell populations. Here we use genetic labelling techniques to separate molecular events occurring in the trophoblast from those in the mesodermal layers of the placenta. In combination with conditional targeting, we show that the imprinted gene Dlk1 is a key player in providing nutrients to the embryo by controlling the placental surface area available for nutrient exchange, and by modulating the production of placental hormones that promote maternal nutrient provision in pregnancy.
• A Novel Syngeneic Mouse Model of Metastatic Hormone-Sensitive Prostate Cancer Provides a Platform for Studying Combination Immunotherapy
  GSE312104Mus musculus16 个样本2026-10-26

  Immunocompetent, hormone-sensitive models of metastatic prostate adenocarcinoma remain limited. We established PL051, a syngeneic luciferase-labeled cell line derived from a Pten^pc-/-;Lkb1^pc-/- (PTEN/LKB1-deficient) mouse background, and profiled its genome and transcriptome alongside tumors from the progenitor GEMM. Whole-exome sequencing (WES) of matched samples shows that PL051 is genetically near-identical to the primary tumor: we detected only one high-confidence somatic coding variant, and copy-number alterations (CNAs) were minimal, with <20% of the captured exome altered. CNAs were predominantly focal (~1–3 kb) and gene-sparse. To map androgen-receptor (AR) signaling at the transcript level, we performed RNA-seq on PL051 following vehicle, dihydrotestosterone (DHT), enzalutamide, and the DHT+enzalutamide combination. The dataset captures agonist-induced AR target activation and antagonist-associated transcriptional shifts (including cell-cycle effects), providing a resource to interrogate AR pathway dynamics in an immune-competent, metastatic context. Together, these data benchmark PL051 as a faithful, transplantable derivative of the GEMM and supply harmonized genomic and transcriptomic profiles suitable for comparative and mechanistic analyses.
• cinedathodes experiment-Cinedathodes experiment.
  GSE308406Arabidopsis thaliana42 个样本2026-10-26

  2023_03_qs_cinedathodes-cinedathodes experiment-Transcriptomic Profiling of Differentiating Hydathodes after LAM (laser microdissection)-Transcriptome of hydathode development (H samples) kinetics compared to leaf mesophyll (C control samples) using the first leaf of Arabidopsis thaliana, 5 to 11 days after germination.
• Organoids and cortical tubers in Tuberous Sclerosis Complex show non-cell autonomous effects of second hit variants
  GSE294081Homo sapiens10 个样本2026-10-26

  Structural abnormalities are common causes of refractory epilepsy, and while progress has been made in understanding the genetic changes associated with these malformations, the pathogenic mechanisms often remain unclear. Dysregulation of the mechanistic target of rapamycin pathway has been found to contribute to a group of focal cortical dysplasia, and patients with Tuberous Sclerosis Complex often have several of these malformations. We used organoids generated from heterozygous patient-derived induced pluripotent stem cells and added isogenic stem cells with second hit variants to determine whether there are non-cell autonomous effects of the null cells. We found that the presence of null cells during differentiation led to abnormalities in neuronal development, which was due to secreted factors. Furthermore, null cells secreted extracellular vesicles containing proteins that inhibit the transcriptional coactivator, YAP1, and knockdown of one specific factor, AMOT, in null cells rescued neuronal differentiation and YAP1 expression. Finally, we analyzed cell type specific gene expression in malformations in patients with TSC and observed similar patterns of gene expression dysregulation. These data define a novel pathogenic mechanism underlying the development of focal brain malformations.
• EGR1 Binding to a Promoter G-Quadruplex Supports Early TNF Expression
  GSE292945Homo sapiens16 个样本2026-10-26

  G-quadruplexes (G4s) influence chromatin and transcription, but their roles in stimulus-induced rapid gene activation remain incompletely understood. Integration of public transcription-factor ChIP-seq, genome-wide G4 maps, and G4 pull-down/MS identified EGR1 as a G4-associated transcription factor. In vitro binding assays further demonstrated that EGR1 directly interacts with multiple G4 conformations, including parallel MYC G4, hybrid BCL2 G4, and antiparallel telomeric hTel21T18 G4. RNA-seq revealed an EGR1-dependent early LPS-induced inflammatory program. Integration with EGR1 ChIP-seq and G4access profiles prioritized TNF as a promoter-proximal EGR1–G4-associated target. A TNF promoter G4 showed BG4 enrichment and a parallel-like CD signature, and its mutation reduced BG4 signal, EGR1 occupancy, reporter activation, and early LPS-induced TNF expression. G4 ligands further disrupted EGR1 binding to the TNF G4 and reduced TNF expression. These findings reveal a promoter G4-dependent layer of EGR1-mediated TNF activation.