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。

• mRNA and miRNA Sequencing Identifies Increased Oxidative Stress Pathways in a Mouse Model of Ethanol Exacerbation of Colitis
  GSE329630Mus musculus23 个样本2026-10-28

  Alcohol consumption has been found to worsen the pathology of colitis. To elucidate the underlying mechanism, we performed both miRNA and mRNA sequencing of the large intestinal epithelial cells derived from a murine model of alcohol and colitis. Male C57BL/6 received Dextran Sulfate Sodium (DSS) for 5 days to induce colitis and gavaged with alcohol (~3g/kg) or water for 3 days. Three hours after the final gavage, the mice were euthanized and colon lengths were measured, followed by epithelial cell isolation. RNA, including miRNA, was isolated from the colonic epithelial cells and sent to Novogene for mRNA and miRNA sequencing. Analysis comparing DSS Ethanol vs Sham Vehicle mice showed 3931 significantly upregulated genes and 3788 significantly downregulated genes. Functional enrichment analysis of GO and KEGG pathways showed enrichment of superoxide anion generation and HIF-1 signaling pathways, both related to oxidative stress. DSS Ethanol compared to DSS Vehicle resulted in 921 significantly upregulated and 1072 significantly downregulated genes (Padj<0.05) with functional enrichment analysis showing the term with the highest fold enrichment was superoxide anion generation. We further confirmed the RNA and protein expression of NOS2, CYBB, and NCF1 which are involved in nitric oxide and superoxide production. miRNA sequencing revealed 84 differentially expressed miRNAs comparing DSS Ethanol to DSS Vehicle. Functional enrichment analysis of predicted targets of these miRNAs also showed enrichment in superoxide anion generation. These results suggest that combined ethanol and DSS exposure may increase the production of reactive oxygen species, which further damages the intestinal lining and potentially contributes to the ethanol exacerbation of colitis
• The Circadian Clock controls Hepatic Inflammation in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD)
  GSE326584Mus musculus24 个样本2026-10-28

  The circadian clock dictates time-of-day dependent gene, protein expression, and metabolite levels to ensure liver homeostasis. Circadian misalignment is implicated in the development of various metabolic disorders, but its contribution to the progression of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) toward Metabolic dysfunction-Associated Steatohepatitis (MASH) remains poorly understood. Here, we aimed to dissect the role of the circadian clock in MASH development. Using an environmental model of chronic circadian misalignment, combined with metabolic and immune phenotyping, single nuclei transcriptomics and lipidomic profiling, we investigated the role of the clock in MASLD development and hepatic inflammation. To dissect the specific contribution of the immune clock, we used a genetic model overexpressing the clock component Rev-erbα in myeloid cells. Chronic circadian misalignment combined with a high-fat, high-sucrose, cholesterol-enriched (HFHSC) diet markedly amplified hepatic inflammation, characterized by the upregulation of pro-inflammatory genes and increased immune cell infiltration, including the expansion of lipid-associated macrophages (LAMs). Although circadian misalignment did not worsen glucose intolerance or hepatic steatosis, it altered hepatic metabolic gene expression, reflecting a broad reprogramming of immune and metabolic pathways. The circadian clock controls both FA profile and inflammatory process, and its misalignment aggravates MASLD by increasing liver inflammation. Targeting circadian regulators such as Rev-erbα in myeloid cells may offer a promising therapeutic avenue for controlling liver inflammation in MASLD.
• Med1 Deletion Reprograms Dental Epithelium into Primitive Hair-Forming Epidermal Architecture via Trp63 Driven Epigenetic Mechanisms
  GSE316208Mus musculus12 个样本2026-10-28

  Ectodermal fate decisions between tooth enamel and skin hair are governed by transcription factors, epigenetic mechanisms, and tissue architecture. Deletion of the Mediator subunit Med1, which links enhancer activity to transcriptional output, induces a striking lineage conversion characterized by ectopic hair formation in mouse incisors. Here, we define the cellular, transcriptional, and epigenetic mechanisms underlying this process. Single-cell and spatial transcriptomic analyses reveal extensive remodeling of the incisor epithelium following Med1 deletion, whereby dental pre-ameloblasts and SI cells convert into hair germ–like populations resembling ancestral hair-initiating cells while retaining dental identity. Epidermal fate is driven by the master regulator Trp63, enabling hair formation without follicles distinguishing this process from canonical skin hair regeneration. Mechanistically, epigenetic changes occur in which TRP63 co-localized with alternative MED12-containing enhancers to activate itself and downstream epidermal genes. Together, these findings suggest that Med1 loss promotes hair formation through unique reprogramming to an evolutionarily primitive epidermal state rather than direct trans-differentiation to skin epithelium, providing new insights in ectodermal plasticity.

  单细胞空间转录组
• Dual SGLT1 and 2 inhibition with sotagliflozin decreases oxidative stress in mice with hypertrophic cardiomyopathy due to tropomyosin E180G mutation
  GSE315790Mus musculus21 个样本2026-10-28

  Background. Hypertrophic cardiomyopathy (HCM) is associated with mitochondrial dysfunction and oxidative stress. Our goal was to determine the effects of the dual SGLT1 and SGLT2 inhibitor sotagliflozin (SOTA) on myocardial remodeling, diastolic function, mitochondrial gene expression and oxidative stress in mice with HCM due to the tropomyosin E180G mutation (E180G). Methods. Male E180G and non-carrier (NC) mice 7-8 weeks old were randomized to SOTA formulated in the chow (30 mg/kg chow) or control diet (CD) for 8 weeks. Cardiac structure and function were assessed by echocardiography at baseline, and after 4 and 8 weeks of treatment. At 8 weeks mice were sacrificed to assess myocardial histology, RNA expression, oxidative stress and oxidative sulfonylation of sarcoplasmic reticulum calcium ATPase (SERCA). Results. At baseline E180G mice had myocardial hypertrophy, interstitial fibrosis, diastolic dysfunction and atrial enlargement - all of which worsened over the next 8 weeks. In E180G mice treatment with SOTA for 8 weeks prevented further LV hypertrophy and atrial enlargement, decreased interstitial fibrosis and normalized diastolic function. Mitochondrial gene sets were downregulated, and oxidative stress was increased and associated with oxidative sulfonylation of SERCA at C674. SOTA treatment upregulated mitochondrial gene sets and prevented the increases in oxidative stress and SERCA oxidation. Upregulated fibrosis gene sets in E180G hearts were not affected by SOTA. Conclusion. In E180G HCM mice downregulation of mitochondrial gene sets is associated with increased oxidative stress and oxidative modification of SERCA. In E180G hearts, SOTA corrected the HCM phenotype, normalized diastolic function, upregulated mitochondrial gene sets, and decreased oxidative stress and SERCA oxidation. Upregulation of mitochondrial gene sets leading to improved mitochondrial function may improve energetics and decrease oxidative stress. Oxidative stress leads to oxidative modification of SERCA and stimulation of fibrosis pathways which may play a significant role in HCM, and thus provide an opportunity for therapeutic intervention with agents that improve mitochondrial function and/or decrease oxidative stress.
• Electroconductive Patch Promotes Heart Repair by Directing Epicardial Cell Fate towards Endothelial Lineage
  GSE311450Mus musculus10 个样本2026-10-28

  By developing patches whose electroconductivity matches native myocardium (cardiac electroconductivity-matched patches, CemPs), we show that WT1⁺ EPDCs convert into functional endothelial cells within 14 days of MI, and increase infarct vascular density in adult mice.We employed genetic fate-mapping approaches in WT1CreERT2 H11ZsGtd mice to trace the origin of the newly generated endothelial cells, and combined with single-cell transcriptomics further identifies a previously uncharacterized transitional state cells which is voltage-sensitive and commits to the endothelial lineage via TRPC3–Ca²⁺ signaling.This work elucidates the relationship between the electrical conductivity of biomaterials and the endothelial differentiation potential of WT1⁺ EPDCs, clearly defining the cellular origin of electroconductive patch-induced angiogenesis in adult mammals post-MI.

  单细胞
• Mitochondrial ATP production promotes T cell differentiation and function by regulating chromatin accessibility [RNASeq3]
  GSE310052Mus musculus12 个样本2026-10-28

  Immune elimination of chronic infection or cancer requires cytotoxic CD8 T cells that adopt and maintain an effector phenotype. Cytotoxic T cell function is a bioenergetically demanding process and T cells subjected to chronic antigen exposure have compromised effector function despite high rates of glycolysis. Here we report the ability of the short chain fatty acid, D-α-hydroxybutyrate, to act as a signaling molecule that increases mitochondrial ATP production and drives the conversion of proliferating T cells into cytotoxic effector cells. DAHB signaling switches ATP production from glycolysis to fatty acid oxidation, even in glucose-replete media. This conversion suppresses both AMPK phosphorylation and the integrated stress response (ISR) in activated T cells while significantly elevating the level of the phosphagen, phosphocreatine (PCr). Both the PCr bioenergetic reserve and oxidative phosphorylation were required for T cell effector differentiation. DAHB-induction of CD8-effector gene transcription was coupled to bioenergetics by enhanced ATP-dependent remodeling of chromatin accessibility at effector gene loci. DAHB enhanced CD8 T cell antitumor activity both in vitro and in vivo, and DAHB treatment of transferred T cells led to persistent in vivo antitumor effects. Together, these findings link cellular bioenergetics to the regulation of chromatin accessibility and gene expression required to support effector function.
• Alternative splicing plays an important role in fast chemical reprogramming [CUT&Tag]
  GSE292985Mus musculus12 个样本2026-10-28

  To investigate the role of Ptbp3 during reprogramming, CUT&Tag was carried out from the reprogramming intermediates transfected with shNC or shPtbp3.
• Muscles transcriptomic response to exercise
  GSE287162Mus musculus12 个样本2026-10-28

  The main goal of study was to see the transcriptional response to acute exercise in mice . For this the RNA seq was done in WT rest and WT exercise. We then want to reproduce the same result in HDAC3 ko mice and found the same result. Tissues were harvested immediately after the last session. RNA-seq identified that most differentially expressed genes (DEGs, exercise vs. rest) were upregulated upon exercise. We observed similar results in wild-type (WT) mice comparing exercise vs. rest and found that exercise-induced activation is independent of HDAC3, supporting the rationale for our investigation and demonstrate the robustness and reproducibility of the results that exercise-induced activation of our target gene is independent of HDAC3
• Lipid nanoparticle-mediated TFEB mRNA delivering for treatment of non-alcoholic fatty liver disease
  GSE283076Mus musculus16 个样本2026-10-28

  Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by excessive lipid accumulation in the liver, often accompanied by obesity and insulin resistance. As the disease progresses, it can lead to non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and even hepatocellular carcinoma. The excessive activation of the mTORC1 complex promotes TFEB phosphorylation, thereby suppressing the TFEB-dependent lysosomal autophagy pathway and contributing to the development of NAFLD. Therefore, pharmacological activation of TFEB may offer a potential therapeutic strategy for NAFLD. However, currently, there is no drug that can directly activate TFEB. While mTORC1 inhibitors can indirectly activate TFEB, their use is limited by systemic side effects. In this study, we utilized lipid nanoparticles (LNP) to deliver TFEB mRNA to the liver. This targeted approach enhanced TFEB expression in hepatic cells, promoted autophagy, and mitigated NAFLD progression in a murine model.
• Effect of YAP and KLF4 overexpression on gene expression of cerebral microvascular endothelial cells [RNA-Seq]
  GSE280201Mus musculus12 个样本2026-10-28

  Our preliminary findings revealed that YAP acts with KLF4. We here report overexpression of YAP and KLF4, either individually or in combination, led to significant changes in the transcriptomic profiles. YAP and KLF4 have substantial overlaps on co-regulation gene, which has a potential synergistic effect on gene expression. Our findings suggest that the co-regulated DEGs play pivotal roles in vascular and cellular processes, highlighting the synergistic effects of YAP and KLF4 on these biological activities.
• CCM2 knockout promotes transcriptional activity of YAP and KLF4 [CUT&Tag]
  GSE280200Mus musculus12 个样本2026-10-28

  CCM2 knockout dramatically increased the number of KLF4 regulatory genes, and similarly, the number of YAP regulatory genes surged. Consistently, the number of genes co-regulated by KLF4 and YAP also increased after CCM2 loss. Upon performing functional analyses of the genes co-regulated by KLF4 and YAP, we found that the genes in WT primary MBMECs were unable to enrich specific signaling pathways, while the genes in Ccm2-knockout primary MBMECs were enriched in several pathways, including SMAD binding, Rho GTPase binding, kinase regulator activity, et al
• Transcriptomic analysis of mucosal immunity in mouse lung tissues induced by sequential Sad23L-RSV vaccination
  GSE352070Mus musculus15 个样本2026-10-27

  We performed transcriptomic analysis of lung tissues from BALB/c mice vaccinated with a novel adenovirus-vectored RSV vaccine (Sad23L-RSV) via an intranasal prime/intramuscular boost regimen. Lung tissues were collected at days 0, 2, 7, and 28 after the booster immunization to investigate the molecular mechanisms of durable mucosal immunity.
• Macrophage lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348147Mus musculus16 个样本2026-10-27

  Glioblastoma (GBM) is characterized by diffuse infiltration into the surrounding brain, limiting complete surgical resection, the strongest determinant of patient survival. The mechanisms driving this invasive growth remain incompletely understood. Here, we identify a lipid-mediated paracrine signaling axis through which tumor-associated microglia/macrophages promote glioma invasion. Integrating single-cell transcriptomics, spatial lipidomics, and functional perturbation across mouse models and human GBM samples, we show that invading tumor cells engage and reprogram myeloid cells via CSF1R–PI3K signaling. This induces lipid metabolic reprogramming and secretion of bioactive lipids, including lysophosphatidylcholines (LPCs) and lysophosphatidic acids (LPAs), which promote GBM invasion through distinct downstream pathways. Disruption of this myeloid–GBM axis, reduces lipid secretion and suppresses invasion. Targeting downstream LPA–LPAR or YAP/TAZ signaling further constrains invasion in a context-dependent manner. Together, these findings define a lipid-driven circuit linking the tumor microenvironment to glioma invasion and identify strategies to reduce infiltration and improve surgical resection.

  单细胞空间转录组扰动筛选
• C-Met controls CD8+ T cell-mediated anti-tumor immunity
  GSE319458Mus musculus12 个样本2026-10-27

  The hepatocyte growth factor (HGF)/c-Met axis is a major oncogenic pathway, yet how it shapes cytotoxic T cell function remains unclear. Here, we show that c-Met identifies a transcriptionally and functionally distinct subset of tumor-reactive CD8⁺ T cells, while HGF suppresses their effector function. Using Pmel-1 CD8⁺ T cells and a CD8⁺ T cell–specific c-Met knockout, RNA sequencing revealed c-Met⁺ CTLs are enriched for cytotoxic, interferon, TCR signaling, and inflammatory programs, whereas HGF induces immunoregulatory pathways, including IL-13–STAT3/STAT6, and downregulates effector genes. Functionally, c-Met⁺ CTLs displayed enhanced antigen-specific killing and superior tumor control, with increased degranulation and lower inhibitory checkpoint expression. HGF or c-Met deficiency restrained these responses. These findings identify c-Met as a marker of highly cytotoxic CD8⁺ T cells and reveal HGF as a key suppressor of CTL function in cancer providing a mechanistic framework for HGF-driven immune suppression in cancer.
• CEBPA-Induced Trophectoderm-like Cells from Pluripotent Stem Cells Enable Modeling of Trophoblast Lineage Specification
  GSE315751Mus musculus28 个样本2026-10-27

  Trophoblast lineages are essential for placental development and play indispensable roles in mammalian development. However, the regulatory mechanisms governing trophoblast lineage specification, particularly trophectoderm formation, remain elusive. Here, we show that transient overexpression of the transcription factor Cebpa in mouse pluripotent stem cells efficiently generates trophectoderm-like cells that recapitulate key transcriptional features of trophectoderm. These trophectoderm-like cells can be further induced to form trophoblast organoids and exhibit developmental competence to generate all trophoblast lineages in vitro. Mechanistically, Cebpa overexpression drives extensive epigenetic reprogramming toward a trophectoderm-like state, including global remodeling of chromatin accessibility and coordinated changes in H3K4me3 and H3K27me3 histone modifications. CUT&RUN analyses further reveal binding of CEBPA to multiple trophectoderm-specific enhancers. Together, our findings identify Cebpa as a potent inducer of trophectoderm potential and establish a new platform for modeling trophectoderm lineage specification in vitro.
• CEBPA-Induced Trophectoderm-like Cells from Pluripotent Stem Cells Enable Modeling of Trophoblast Lineage Specification [RNA-Seq]
  GSE315750Mus musculus14 个样本2026-10-27

  Trophoblast lineages are essential for placental development and play indispensable roles in mammalian development. However, the regulatory mechanisms governing trophoblast lineage specification, particularly trophectoderm formation, remain elusive. Here, we show that transient overexpression of the transcription factor Cebpa in mouse pluripotent stem cells efficiently generates trophectoderm-like cells that recapitulate key transcriptional features of trophectoderm. These trophectoderm-like cells can be further induced to form trophoblast organoids and exhibit developmental competence to generate all trophoblast lineages in vitro. Mechanistically, Cebpa overexpression drives extensive epigenetic reprogramming toward a trophectoderm-like state, including global remodeling of chromatin accessibility and coordinated changes in H3K4me3 and H3K27me3 histone modifications. CUT&RUN analyses further reveal binding of CEBPA to multiple trophectoderm-specific enhancers. Together, our findings identify Cebpa as a potent inducer of trophectoderm potential and establish a new platform for modeling trophectoderm lineage specification in vitro.
• Endogenous variability in transcription factor concentrations shapes their genome-wide occupancy [ChIP-seq]
  GSE308325Mus musculus44 个样本2026-10-27

  The control of transcription factor (TF) concentrations is crucial for the precise regulation of gene expression and cell fate decisions during development. Yet, TF concentrations can display substantial temporal fluctuations and intercellular variations. How TF levels quantitatively shape genome-wide occupancy patterns remains largely unexplored. Here, we systematically investigate how physiological fluctuations in the concentrations of the pluripotency TFs OCT4, SOX2, and NANOG impact their genomic binding profiles in mouse embryonic stem cells. We uncover distinct concentration-dependent binding behaviors for each TF. NANOG occupancy increased monotonously with its concentration, even though a common set of regions made accessible by OCT4 and SOX2 were highly and uniformly bound at all NANOG concentrations. In contrast, SOX2 occupancy does not increase with its concentrations, while OCT4 displayed an intermediate behavior. Our results challenge the notion that TF binding follows simple mass-action dynamics and reveal a core set of pluripotency regions that are bound by all three TFs at all TF concentrations, revealing how pluripotency can be maintained despite marked fluctuations in core pluripotency TFs.
• A GABA-producing Limosilactobacillus fermentum ameliorates autism-like behaviors associated with altered gut microbial metabolism and cortical GABA signaling
  GSE351532Mus musculus24 个样本2026-10-26

  Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social deficits and restricted, repetitive behaviors. Altered excitation/inhibition (E/I) balance, including impaired γ-aminobutyric acid (GABA) ergic signaling, has been implicated as a key pathophysiological feature of ASD. Although growing evidence implicates the gut–brain axis in regulating neural function, the strain-specific microbial mechanisms that influence central GABAergic signaling remain incompletely understood. Here, we evaluated whether Limosilactobacillus fermentum IMB064, identified by genome-based in silico screening, could modulate ASD-associated symptoms in BTBR mice, a widely used ASD model. Oral administration of IMB064 significantly reduced repetitive behaviors and improved social novelty preference in BTBR mice. Taxa-resolved metabolic flux modeling of the gut microbiome based on metagenomic profiling indicated that IMB064 administration was associated with alterations in gut microbial metabolic potential, including increased potential for GABA production, particularly among GABA-producing taxa such as Limosilactobacillus. Transcriptomic analysis further revealed a cortex-selective response to IMB064, with 1,552 cortical genes significantly altered and enriched in neuronal signaling pathways. These differentially expressed genes significantly overlapped with human ASD-associated cortical co-expression modules identified by weighted gene co-expression network analysis (WGCNA) and with chromatin-regulatory gene networks. Consistent with this region-specific molecular response, IMB064 significantly increased cortical GABA levels, with a trend toward an increased GABA-to-glutamate ratio, whereas no significant changes were observed in the striatum. Collectively, these findings indicate that the GABA-producing strain IMB064 alters gut microbial metabolic potential and is associated with cortex-selective changes in GABA-related neurochemical profiles, accompanied by modulation of human ASD-relevant gene networks and improvement of ASD-like behavioral phenotypes, supporting IMB064 as a promising live biotherapeutic candidate for ASD.

  计算与 AI
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses [CUT&Run]
  GSE351044Mus musculus18 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.
• Gene therapies alleviate absence epilepsy associated with Scn2a deficiency in DBA/2J mice
  GSE349370Mus musculus10 个样本2026-10-26

  Loss-of-function (LoF) mutations in SCN2A, encoding the voltage-gated sodium channel NaV1.2, cause severe, often drug-resistant epilepsy. We generated Scn2agt/gt mice on the seizure-susceptible DBA/2J (D2J) background and identified prominent spontaneous absence seizures with short and long spike-wave discharges (SWDs), contrasting with the milder phenotype observed on the seizure-resistant C57BL/6N background. Restoring NaV1.2 expression in adult mice markedly reduced SWDs, supporting the potential of adult SCN2A gene replacement. RNA sequencing revealed broad downregulation of voltage-gated potassium channel genes, including Kcnal (KV1.1), which was also reduced in human cerebral organoids with SCN2A deficiency. AAV-mediated expression of human KV1.1 substantially reduced absence seizures in Scn2agt/gt mice. These findings demonstrate the influence of genetic background on SCN2A-associated epilepsy and identify NaV1.2 replacement and KV1.1 augmentation as potential therapeutic strategies.
• 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
• 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.
• 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.
• 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.