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。

• Adipose mitochondrial functional enhancement via DsbA-L rewires systemic aging through an adipokine-mediated longevity pathway
  GSE351767Mus musculus4 个样本2026-10-27

  Mitochondrial dysfunction is a hallmark of aging, but whether restoring mitochondrial function in adipose tissue alone can delay systemic aging is unknown. Here we show that adipose-specific upregulation of the mitochondrial chaperone DsbA-L in mice improves metabolic and cognitive function and extends lifespan, linking adipose mitochondrial fitness directly to systemic aging. DsbA-L upregulation reprograms adipose gene expression and raises circulating levels of the adipokine Serpina3m. Fat-body-specific knockdown of Spn42De (CG9460), the Drosophila serpin counterpart of Serpina3m, shortens lifespan, whereas its overexpression extends it. SERPINA3, the human ortholog, is enriched in centenarians. Unlike conventional mitochondrial enhancers, DsbA-L couples metabolic efficiency to endocrine signaling, and berberine increases DsbA-L expression, indicating that this pathway is pharmacologically tractable. These benefits occur in both sexes and identify DsbA-L–Serpina3m signaling as a target for healthy aging.
• Transcriptomic profiling of mouse bone marrow neutrophils treated with Propionibacterium acnes with or without human umbilical cord blood mesenchymal stem cell-derived exosomes
  GSE351531Mus musculus8 个样本2026-10-27

  This study investigates transcriptional responses of mouse bone marrow neutrophils to human umbilical cord blood mesenchymal stem cell-derived exosomes during Propionibacterium acnes stimulation. Bulk RNA sequencing was performed on neutrophils exposed to P. acnes alone or to P. acnes together with exosomes. The dataset comprises eight samples and includes paired-end sequencing reads, gene-level read counts, and FPKM expression values. It supports investigation of inflammatory responses and pathways associated with neutrophil extracellular trap formation.
• Microglial lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348401Mus musculus8 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
• 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
• Glioma regulates GABAergic signaling to drive hyperactivity and tumor progression [RNA-seq]
  GSE348105Mus musculus6 个样本2026-10-27

  Recent studies identified bi-directional communication between neurons and glioma tumors as a key driver of hyperexcitability and malignant progression. While much of this work has focused on the activity of excitatory neurons, roles for inhibitory neurons remain poorly defined. Using in-vivo screening approaches in autochthonous glioma models, we found that loss of a GABA transporter (Slc6a1) enhanced glioma progression, promoted network hyperactivity, and influenced tonic GABA release by tumors. Mechanistically, we show that glioma tumors influence the activity of inhibitory neurons and their subsequent stimulation suppresses tumor growth. Further screening of these phenomena identified Diazepam Binding Inhibitory (DBI), a secreted negative allosteric modulator of GABA-A, as a link between glioma related hyperexcitability and proliferation that functions through modulating inhibitory neuronal signaling. Collectively, our findings indicate that glioma tumors utilize multiple mechanisms to manipulate the activity of inhibitory neurons as a means to drive network hyperactivity, which ultimately facilitates malignant progression.
• Glioma regulates GABAergic signaling to drive hyperactivity and tumor progression
  GSE348034Mus musculus4 个样本2026-10-27

  Recent studies identified bi-directional communication between neurons and glioma tumors as a key driver of hyperexcitability and malignant progression. While much of this work has focused on the activity of excitatory neurons, roles for inhibitory neurons remain poorly defined. Using in-vivo screening approaches in autochthonous glioma models, we found that loss of a GABA transporter (Slc6a1) enhanced glioma progression, promoted network hyperactivity, and influenced tonic GABA release by tumors. Mechanistically, we show that glioma tumors influence the activity of inhibitory neurons and their subsequent stimulation suppresses tumor growth. Further screening of these phenomena identified Diazepam Binding Inhibitory (DBI), a secreted negative allosteric modulator of GABA-A, as a link between glioma related hyperexcitability and proliferation that functions through modulating inhibitory neuronal signaling. Collectively, our findings indicate that glioma tumors utilize multiple mechanisms to manipulate the activity of inhibitory neurons as a means to drive network hyperactivity, which ultimately facilitates malignant progression.
• Molecular Imaging of the TGF-β Activating Integrin avb6 Detects Chronic Lung Allograft Dysfunction
  GSE346597Mus musculus2 个样本2026-10-27

  TGF-β-activating integrins promote solid-organ fibrosis, suggesting their potential as disease markers. Chronic lung allograft dysfunction (CLAD), a progressive fibrotic complication that limits lung transplant survival, is driven by intragraft TGF-β activation. However, TGF-β-activating integrin expression patterns remain undefined in lung transplants. Single-cell RNA sequencing and proteomic analysis of tissue specimens from a mouse CLAD model and human explanted lungs with CLAD revealed high levels of the TGF-β-activating integrin αvβ6, primarily localized to fibrosis-associated Keratin 8+ alveolar transitional epithelial cells, which were greatly reduced in tolerant lungs. Molecular imaging with a newly optimized positron emission tomography radiotracer specific for avb6, [64Cu]Cu-DOTA-A20-K16R, showed significantly higher uptake in CLAD than in tolerant transplants. [64Cu]Cu-DOTA-A20-K16R activity was also reduced by experimental treatments that lowered avb6 expression and inhibited CLAD severity. Finally, [64Cu]Cu-DOTA-A20-K16R autoradiographic analysis of human explanted lungs with CLAD showed elevated activity that correlated with increased avb6 expression. Collectively, these findings illustrate the potential utility of αvβ6 molecular imaging for detecting CLAD pathogenesis.

  单细胞
• Single-cell profiling of microglia transcriptomes transduced by the AAV-MSRE tool
  GSE345675Mus musculus9 个样本2026-10-27

  This study profiles the transcriptomic responses of microglia transduced with the AAV-MSRE tool at single-cell resolution. Single-cell RNA sequencing was used to characterize transduced microglial populations, assess their molecular identities, and evaluate transcriptional changes associated with AAV-MSRE delivery. These data provide a resource for examining the cellular specificity and transcriptomic impact of AAV-MSRE-mediated targeting in microglia.

  单细胞
• Transcriptomic profiling of M1-like and M2-like mouse bone marrow-derived macrophages
  GSE344431Mus musculus6 个样本2026-10-27

  Macrophage activation states are involved in intestinal inflammation and tissue remodeling, but the transcriptional programs linking macrophage polarization to ulcerative colitis-associated molecular changes remain incompletely characterized. In this study, primary bone marrow-derived macrophages from mice were polarized toward M1-like or M2-like states and subjected to bulk RNA sequencing. M1-like polarization was induced using lipopolysaccharide and interferon-gamma, whereas M2-like polarization was induced using interleukin-4 and interleukin-13. Three biological replicates were analyzed per group. The resulting transcriptomes were used to identify macrophage polarization-related genes and were subsequently integrated with ulcerative colitis macrophage single-cell transcriptomic and circulating proteomic evidence to prioritize disease-associated macrophage candidates.

  单细胞
• 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.
• A single cell atlas defines perinatal factors that drive murine bone marrow development
  GSE318094Mus musculus2 个样本2026-10-27

  Processes that direct initial colonization and maturation of the bone marrow remain elusive, despite their importance to lifelong hematopoiesis. Bone marrow mesenchymal and stromal cell (BMSC) maturation must establish supportive hematopoietic niches prior to the recruitment and colonization of hematopoietic stem cells (HSCs). Here, we define the identity of murine BMSC progenitors and temporal nature of marrow colonization through a single cell atlas spanning late gestation through 18 months of age. We define progenitor cells and developmental trajectories for Cxcl12-abundant reticular (CAR) cells and osteoblasts within the marrow, including the emergence of direct and secreted signaling modalities that impact HSC quiescence and regenerative capacity. We further identify temporal changes in Early B Cell Factor (Ebf) 1-3 transcription factor expression and activity that correlate with niche establishment. These transcriptional activities relate to change to changes in systemic physiology, including metabolic, inflammatory, and hypoxic signaling, that direct CAR cell emergence after birth in mice. These findings provide unprecedented resolution to the colonization and maturation of the murine bone marrow environment.

  单细胞细胞图谱
• CEBPA-Induced Trophectoderm-like Cells from Pluripotent Stem Cells Enable Modeling of Trophoblast Lineage Specification [scRNA-Seq]
  GSE315752Mus musculus1 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.

  单细胞
• 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 [ATAC-seq]
  GSE308326Mus musculus8 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.
• 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.
• Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptome profile in ileum tissue from mice infected with C. parvum at days 3 post-infection.
  GSE272799Mus musculus6 个样本2026-10-27

  Cryptosporidium spp., an apicomplexan protozoan, is one of the most common pathogens responsible for moderate-to-severe diarrhea in children under 2-year-old. Metabolic dysregulation in host following Cryptosporidium infection remains obscure. In the current study, we analyzed the transcriptome of ileal epithelium from mice infected with C. parvum to identify potential genes involved in metabolic reprogramming. Total RNA was collected for the genome-wide analysis, for sequencing using BGISEQ-500 platform.
• Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptome profile in liver tissue from mice infected with C. parvum at days 3 post-infection.
  GSE234579Mus musculus6 个样本2026-10-27

  Cryptosporidium spp., an apicomplexan protozoan, is one of the most common pathogens responsible for moderate-to-severe diarrhea in children under 2-year-old. Metabolic dysregulation in host following Cryptosporidium infection remains obscure. In the current study, we analyzed the transcriptome of liver tissue from mice infected with C. parvum to identify potential genes involved in metabolic reprogramming in the liver. Total RNA was collected for the genome-wide analysis, for sequencing using BGISEQ-500 platform.
• 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.
• Novel WRN Exon 10 Skipping Mutation Triggers Progerin Accumulation and Premature Aging
  GSE351663Mus musculus6 个样本2026-10-26

  Werner Syndrome (WS) is an autosomal recessive disorder characterized by premature aging and increased susceptibility to various age-related diseases, predominantly caused by mutations in the WRN gene. This study investigated a Chinese patient with WS and partial lipoatrophic diabetes mellitus, aiming to identify a novel pathogenic variant in the WRN gene. High-throughput sequencing was conducted on genomic DNA from a blood sample. The identified homozygous variant (WRN_intron9 c.1270-1G>C) was confirmed, and its pathogenicity was assessed through in silico predictions, structural modeling, and cell function assays. The variant's effect on exon skipping was analyzed, and cellular assays were performed to validate the induced phenotype. The study identifies a novel WRN variant as a potential pathogenic factor in the patient. Simulations predict that the WRN_intron9 c.1270-1G>C mutation triggers exon 10 skipping, deleting one of the two highly homologous peptide regions encoded by exon 10 and exon 11 respectively. Cellular assays confirm senescent phenotype induction and human progerin accumulation, leading to premature cellular senescence.

  计算与 AI
• 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
• 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
• IGF1R-derived glycolysis maintains primordial follicle survival in neonatal mouse ovaries
  GSE351522Mus musculus6 个样本2026-10-26

  In mammals, the primordial follicle pool is essential for sustaining female fertility. In the present study, insulin-like growth factor 1 (Igf1) was found to be markedly low in neonatal mouse ovaries relative to its dramatic expression in the liver, whereas Igf2 exhibited high expression levels in both neonatal ovarian and hepatic tissues. IGF1 receptor (IGF1R) was mainly localized in the pre-granulosa cells and oocytes of mouse primordial follicles. IGF1R inhibitors ADW-742 and AEW-541 significantly decreased the number of primordial and growing follicles in cultured neonatal mouse ovaries. Further studies revealed that ADW-742 decreased glycolysis-related gene expression and amino acid levels in neonatal mouse ovaries, and caused mitophagy in pre-granulosa cells and autophagic flux blockade in oocytes of primordial follicles. Enhanced glycolysis by short-term pyruvate-free treatment and/or signal transducer and activator of transcription 3 (STAT3) activator colivelin increased amino acid levels and partially reversed ADW-742-induced mitophagy and follicle apoptosis. Finally, ADW-742 also induced autophagy in human oocytes. Thus, IGF/IGF1R maintains the survival of primordial follicles through glycolysis. These findings offer novel insights into the mechanisms underlying the maintenance of female mammalian fertility.
• 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.
• RNA Polymerase II Dynamics in Antiviral NK Cell Responses [Pol II ChIP-Seq]
  GSE351024Mus musculus2 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
• CCL11 regulates microglial responses in aged mice following ICH.
  GSE344735Mus musculus6 个样本2026-10-26

  CCL11 level increases in circulation with age, with the ability to penetrate the brain, where it attenuates homeostatic functions. Microglia (MG) are essential brain tissue macrophages, and are critical for improved ICH outcomes. To study the effect of systemic-neutralization of CCL11 in aged mice, particularly on MG gene expression changes following ICH injury, we performed RNA-sequencing of MG collected after experimental ICH in a mouse blood injection model. We intraperitoneally administered an anti-CCL11 antibody to aged male mice prior to ICH, isolated MG from the ipsilateral hemisphere, and used the MG for bulk RNA-sequencing analysis. We found that sequestration of CCL11 in the circulation of aged mice prior to ICH upregulates the expression of microglial genes linked to pro-phagocytic, anti-oxidative, and anti-inflammatory signaling.
• TNFR2 agonism increases tissue and effector Treg cells
  GSE344625Mus musculus2 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
• The antioxidant (+)-Catechin reduces inflammation and promotes a stable plaque phenotype in female LDL receptor deficient mice fed a high-fat diet via anti Inflammatory and smooth muscle cell regulatory pathways
  GSE342632Mus musculus6 个样本2026-10-26

  Nutraceuticals such as (+)-Catechin are emerging as promising agents for the prevention and treatment of atherosclerotic cardiovascular disease. A large prospective study of 34,492 participants previously demonstrated an inverse association between (+)-Catechin intake and risk for coronary heart disease. Our recent work further showed that (+)-Catechin inhibits several atherosclerosis related processes in vitro, induces beneficial metabolic changes in male C57BL/6J mice fed a high fat diet (HFD), and reduces plaque burden and inflammation in male low-density lipoprotein (LDL) receptor deficient (LDLr / ) mice fed a HFD. Given known sex specific differences in atherosclerosis, it is essential to extend these investigations to female mice. The objective of this study was therefore to investigate the effects of (+)-Catechin in female LDLr / mice in vivo. (+)-Catechin lowered plasma cholesterol levels, reduced circulating T cell populations, and increased several beneficial short chain fatty acids in both the plasma and the faeces. It also decreased plaque size, lipid content, macrophage accumulation, and CD3⁺ T cell infiltration in the aortic root, while enhancing markers of plaque stability. RNA sequencing (RNA seq) of the thoracic aorta revealed modulation of key pathways involved in inflammatory signalling, hypertension and immune responses. Complementary studies in human aortic smooth muscle cells demonstrated that (+)-Catechin attenuated macropinocytosis and oxidised LDL uptake, processes linked to plaque progression, without promoting calcification. RNA seq identified several genes and pathways consistent with the compound’s anti atherogenic and plaque stabilising actions. Collectively, these findings provide new mechanistic insights into the beneficial cardiovascular effects of (+)-Catechin in female mice and support further evaluation of this flavanol in human clinical trials.