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。

• RNA-sequencing of brain endothelial cells from Slc1a1 endothelial cell conditional knockout mice and controls
  GSE346752Mus musculus8 个样本2026-10-30

  The goal of this study was to understand the transcriptional response of brain endothelial cells to a loss of brain endothelial Slc1a1 expression. Sample GSM10039984 (ECs, control, 3) and GSM10039987 (ECs, mutant, 4) were excluded from all published analyses because of separation from its group on principal component analysis. Final analyses used n = 3 per group. The excluded sample is included in this deposition for completeness.
• A CD4-lineage erythro-myeloid progenitor within the adult bone marrow defines an alternative pathway for macrophage generation [scRNA-Seq]
  GSE345262Mus musculus3 个样本2026-10-30

  Tissue-resident macrophages originate from distinct developmental sources, but in adulthood, their replenishment is thought to depend exclusively on circulating monocytes. Here, we identify a previously unrecognized CD4-lineage erythro-myeloid progenitor, termed EMPROR (Erythro-Myeloid Progenitor), that resides in the adult bone marrow and defines an alternative pathway for generating macrophages. EMPROR cells are phenotypically and transcriptionally distinct from hematopoietic stem cells, common myeloid progenitors, and monocyte precursors. They lack expression of Csf1r and Ccr2 while expressing Cd4 and c-Kit. Single-cell RNA sequencing, RNA velocity analysis, and in vitro and in vivo lineage assays demonstrate a multilineage potential encompassing macrophage, neutrophil, megakaryocytic, and erythroid fates. In vivo, EMPROR cells efficiently generate perivascular and tumor-associated macrophages independently of CCR2-mediated monocyte recruitment, and also contribute to erythroid and granulocytic lineages under inflammatory and neoplastic conditions. Transcriptomic comparisons position EMPROR cells closest to embryonic erythro-myeloid progenitors, indicating that an embryonic-like erythro-myeloid program persists within the adult bone marrow. These findings expand current models of adult myelopoiesis and highlight a previously unappreciated developmental pathway that sustains macrophage diversity beyond the classical monocyte lineage.

  单细胞
• CRYAB-driven mitochondrial fission induces senescence to promote adaptive resistance to EGFR-TKI in LUAD brain metastasis
  GSE326531Mus musculus4 个样本2026-10-30

  Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) exhibit limited efficacy against lung cancer brain metastases, often resulting in rapid and inevitable resistance. However, the unique mechanisms driving this brain microenvironment-specific therapeutic failure remain elusive. Here, utilizing in vivo orthotopic models and single-cell RNA sequencing, we reveal that targeted therapy induces a distinct, metabolically hyperactive senescent cell subpopulation that drives rapid EGFR-TKI tolerance in brain metastasis. We identify the molecular chaperone CRYAB as an indispensable driver specifically upregulated within this senescent persister state. Mechanistically, CRYAB physically interacts with VDAC2 at the outer mitochondrial membrane, promoting endoplasmic reticulum (ER)-mitochondria tethering and calcium influx. This CRYAB-VDAC2 axis orchestrates adaptive mitochondrial fission, hyperactivating oxidative metabolism while simultaneously shielding（preventing？） senescent cells from fatal oxidative stress. Genetic or pharmacological blockade of mitochondrial fission completely abolishes CRYAB-mediated therapeutic resistance. Therapeutically, we demonstrate that a 25-hydroxycholesterol (25HC) dietary intervention acts as a potent in vivo senolytic strategy, directly dismantling the CRYAB-dependent resistance network, eradicating senescent persister cells, and synergistically prolonging overall survival when combined with Osi. Furthermore, high baseline CRYAB expression in pre-treatment primary lung biopsies clinically predicts lower intracranial objective response rates and shorter progression-free survival in a cohort of advanced EGFR-mutant NSCLC patients. Collectively, our study uncovers a novel CRYAB-VDAC2-mitochondrial fission axis that enforces therapy-induced senescence and highlights 25HC dietary intervention as a highly translatable combinatorial strategy to overcome EGFR-TKI resistance in brain metastasis.

  单细胞
• Immune cells adapt to distinct stem cell niches to govern tissue homeostasis [scRNA-seq]
  GSE314679Mus musculus2 个样本2026-10-30

  In adult tissues, epithelial stem cells exist within distinct residences, each endowing them with exclusive instructions for regenerative fitness in homeostasis and wound repair. Key components of these ‘niches’ are immune cells, which protect the host against external and internal threats. Whether and how stem cell: immune cell crosstalk contributes to normal tissue homeostasis remains less clear. Here, we discover functional adaptation of lymphocytes within two distinct skin stem cell niches and show that through this communication, each niche adjusts to meet diverse tissue demands. In the upper hair follicle, where microbial load is high, T cells express lymphotoxin-β and stimulate adjacent receptor-positive epithelial stem cells to form an immune-competent niche tailored to control microbial expansion. By contrast, in the epidermis, these T cells produce amphiregulin to maintain stem cell stoking of the skin’s barrier. Concomitantly, they express the immune checkpoint protein ‘LAG3’, which autorestricts lymphocyte numbers, and hence amphiregulin levels, thereby preventing over-proliferative responses. Finally, when epidermal T cells are absent, distinct dermal lymphocytes restore the imbalance by colonizing the niche and activating amphiregulin. Our findings unveil new modes of homeostatic control and functional specialization of immune-stem cell niches, tailoring them to suit the demands of distinct tissue microenvironments.

  单细胞
• Immune cells adapt to distinct stem cell niches to govern tissue homeostasis [bulkRNA-seq]
  GSE314678Mus musculus4 个样本2026-10-30

  In adult tissues, epithelial stem cells exist within distinct residences, each endowing them with exclusive instructions for regenerative fitness in homeostasis and wound repair. Key components of these ‘niches’ are immune cells, which protect the host against external and internal threats. Whether and how stem cell: immune cell crosstalk contributes to normal tissue homeostasis remains less clear. Here, we discover functional adaptation of lymphocytes within two distinct skin stem cell niches and show that through this communication, each niche adjusts to meet diverse tissue demands. In the upper hair follicle, where microbial load is high, T cells express lymphotoxin-β and stimulate adjacent receptor-positive epithelial stem cells to form an immune-competent niche tailored to control microbial expansion. By contrast, in the epidermis, these T cells produce amphiregulin to maintain stem cell stoking of the skin’s barrier. Concomitantly, they express the immune checkpoint protein ‘LAG3’, which autorestricts lymphocyte numbers, and hence amphiregulin levels, thereby preventing over-proliferative responses. Finally, when epidermal T cells are absent, distinct dermal lymphocytes restore the imbalance by colonizing the niche and activating amphiregulin. Our findings unveil new modes of homeostatic control and functional specialization of immune-stem cell niches, tailoring them to suit the demands of distinct tissue microenvironments.
• Acute Degradation of Pumilio Proteins Reveals a Biphasic Posttranscriptional Regulatory Hierarchy in Embryonic Stem Cell Fate Decision [iCLIP]
  GSE310693Mus musculus8 个样本2026-10-30

  Post-transcriptional regulation is critical for mammalian embryogenesis yet has been underexplored. We previously showed that RNA-binding Pumilio proteins (Pum1/2) are essential for early mouse embryogenesis and embryonic stem cell (ESC) functions. Here, using acute protein degradation systems combined with time-resolved RNA-seq and eCLIP, we delineate a two-phase regulatory hierarchy modulated by Pum1/2 in mouse ESCs. The first phase, occurring within 10 hours of Pum1/2 depletion, is predominantly the stabilization of over 100 Pum1/2-target mRNAs, while the second phase, occurring in subsequent 66 hours, propagates to over 1,000 mRNAs mostly through indirect regulatory effects. Functionally, Pum1/2 depletion delays transition from naïve to formative pluripotency, impairs neuroectoderm differentiation, and enhances germline specification. Mechanistically, Pum1/2 directly repress mRNAs encoding PRC2 subunits, including Suz12, thereby constraining H3K27me3 deposition at neuroectodermal gene loci. These findings establish Pum1/2 as biphasic post-transcriptional regulators of pluripotency and lineage balance and link RNA stability control to chromatin-mediated silencing.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health [Ribo-seq]
  GSE308616Mus musculus4 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives cardiometabolic disease. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage – characteristic of mitochondrial and lipogenic proteins.Together, our findings uncover a conserved translational control mechanism that regulates energy state in cellular metabolism.
• Ribosomal modification by BUD23 drives selective translational control over energy state and metabolic health
  GSE308532Mus musculus9 个样本2026-10-30

  Efficient energy metabolism is essential for health, and its dysregulation drives conditions like cardiometabolic disease and obesity. Delivery of regulatory control through translation and ribosome function is emerging as important. Here, we identify the rRNA methyltransferase BUD23 as a potent regulator of cellular and systemic energy homeostasis. Adipocyte-specific deletion of BUD23 in mice regulates lipid and mitochondrial metabolism resulting in a pronounced lean phenotype and resistance to diet-induced obesity. Mechanistically, BUD23 modulates translation initiation and efficiency of mRNAs with specific features – including short 5’ UTR length and GC-rich post-initiation codon usage - characteristic of mitochondrial and lipogenic proteins. Human genetic analyses and drug-target Mendelian Randomisation support a role for BUD23 in cardiometabolic traits and diseases. Together, our findings uncover a conserved translational control mechanism that regulates energy metabolism and offers a potential therapeutic target.
• Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration [scATAC-seq]
  GSE297937Mus musculus2 个样本2026-10-30

  T cell development progresses through discrete stages that require precise control of gene activation and gene repression. Gene silencing is primarily mediated through epigenetic modifications, mediated by the interaction of transcription factors with repressor complexes containing chromatin-remodeling enzymes. Found within many such complexes, the corepressors NCOR1 and NCOR2 recruit histone deacetylases to suppress transcription of target genes. Using Cd4-cre mice, we identified multiple roles for NCOR1 and NCOR2 throughout thymocyte development. Here, we employed scATAC-seq to examine whether the RNA- and protein-level differences observed in these mice correlate with changes in chromatin accessibility.

  单细胞
• Lymphatic endothelium-restricted synthetic circuit therapy potentiates repair and chemoimmunotherapy response in a surgical lymphedema model
  GSE285323Mus musculus9 个样本2026-10-30

  Lymphedema is a frequent and difficult-to-treat surgical complication of various cancers involving lymph node dissection. Lymphangiogenic factor therapy is not clinically applied due to its pro-tumor effects. Here, our pharmacodynamic analysis and lymphovenous anastomosis intervention show that lymphedema is associated with reduced antitumor immunity in breast cancer patients. AAV delivery of lymphangiogenic factors mediated by Prox1, a LEC promoter, promotes tumor progression because of aberrant Prox1 activities in tumor cells. Therefore, we develop a LEC-specific synthetic circuit, LNCSMD, by adding staufen1-mediated mRNA decay (SMD) elements corresponding to high-throughput-identified tumor-specific lncRNAs. LNCSMD treatment abolishes unwanted outputs in tumor cells, induces lymphatic vessel repair and potentiates chemoimmunotherapy in vivo. We uncover that SMD can be harnessed as off-the-shelf synthetic circuit treatment for lymphedema.
• Nuclear corepressors NCOR1 and NCOR2 entrain thymocyte signaling, selection, and emigration
  GSE246149Mus musculus3 个样本2026-10-30

  T cell development proceeds via discrete stages that require both gene induction and gene repression. Transcription factors direct gene repression by associating with corepressor complexes containing chromatin-remodeling enzymes; the corepressors NCOR1 and NCOR2 recruit histone deacetylases to these complexes to silence transcription of target genes. Earlier work identified the importance of NCOR1 in promoting the survival of positively-selected thymocytes. Here, we used flow cytometry and single cell RNA sequencing to identify a broader role for NCOR1 and NCOR2 in regulating thymocyte development. Using Cd4-cre mice, we found that conditional deletion of NCOR2 had no effect on thymocyte development, whereas conditional deletion of NCOR1 had a modest effect. In contrast, Cd4-cre x Ncor1f/f x Ncor2f/f mice exhibited a significant block in thymocyte development at the DP to SP transition. Combined NCOR1/2 deletion resulted in increased signaling through the T cell receptor, ultimately resulting in elevated BIM expression and increased negative selection. The NF-κB, NUR77, and MAPK signaling pathways were also upregulated in the absence of NCOR1/2, contributing to altered CD4/CD8 lineage commitment, TCR rearrangement, and thymocyte emigration. Taken together, our data identify multiple critical roles for NCOR1/2 throughout thymocyte development.

  单细胞
• Metabolic trapping of arachidonic acid by Treg cells shapes CD8+ T cell anti-tumor immunity
  GSE352441Mus musculus7 个样本2026-10-29

  Regulatory T (Treg) cells rely on lipid metabolism to thrive in the lipid-rich tumor microenvironment (TME), but whether this metabolism shapes the extracellular metabolite landscape that acts on effector T cells remains unknown. Here, we identify epoxide hydrolase 1 (Ephx1), highly expressed in tumor-infiltrating Treg cells, as a cell-intrinsic determinant of arachidonic acid (AA) availability in the TME. Treg-specific deletion of Ephx1 induced compensatory, ACSL4-dependent incorporation of exogenous AA, converting Treg cells into a metabolic trap for tumor-derived AA and lowering its extracellular abundance. The resulting AA scarcity restored the mitochondrial fitness of CD8⁺ T cells, rewired their metabolism away from fatty acid oxidation toward more efficient energy generation, and skewed exhaustion trajectories toward effector-like intermediate states while preserving the stem-like progenitor pool, collectively restraining tumor progression. In patients with hepatocellular carcinoma, TME AA levels tracked with tumor burden and inversely with the mitochondrial fitness of infiltrating CD8⁺ T cells. Accordingly, intratumoral delivery of the AA-release inhibitor Methyl Arachidonyl Fluorophosphonate (MAFP) reinvigorated CD8⁺ T cell immunity and acted synergistically with anti-PD-1 therapy. Targeting Treg cell lipid metabolism thus offers a route to reprogram the TME metabolome and potentiate cancer immunotherapy.
• Prenatal maternal cold stress exposure drives sex-specific neurodevelopmental disruptions in the fetal hypothalamus
  GSE328919Mus musculus3 个样本2026-10-29

  The prevalence of neurodevelopmental disorders (NDDs) is increasing, with growing evidence implicating the intrauterine environment as a critical regulator of fetal brain development. Gestational perturbations such as maternal stress can increase NDD risk; however, the mechanism(s) by which prenatal maternal stress reshape fetal neurodevelopment remain unclear. Accordingly, the objective of my project was to characterize how maternal cold stress exposure during pregnancy disrupts neural stem and progenitor cell (NSPC) developmental programs in the fetus and the impact this has on neurodevelopment in the hypothalamus. Pregnant mice were exposed to 4°C for 30 minutes daily from embryonic day 11.5 (E11.5) to E15.5—a critical period of neurodevelopment in the hypothalamus. To assess how maternal cold stress impacts neural stem cell (NSC) behaviours, we employed the neurosphere assay, quantifying the number and size of primary and secondary neurospheres as a measure of NSC proliferation and self-renewal, respectively. Our findings revealed no change in NSC proliferation or self-renewal when comparing control and maternal cold stress male and female neurospheres. However, differentiation of dissociated NSCs revealed that neurons from both sexes had longer axons following maternal cold stress exposure. Interestingly, only male-derived cultures exhibited a significant increase in the number TUJ1+ neurons in response to maternal cold stress exposure, whereas only female-derived maternal cold stress cultures showed enhanced dendritic arborization. To explore the molecular basis of these changes, we performed single-cell RNA sequencing on E15.5 fetal hypothalamic NSPCs. Analysis of differentially expressed genes uncovered basal sex differences between the transcriptional signatures of control male and female Cycling NSPCs and suggested that maternal cold stress shifts female Cycling NSPCs toward a more male-like transcriptional profile. Gene ontology analysis revealed that maternal cold stress upregulates pathways linked to neuronal growth, development, and GABAergic neuron differentiation, but only in females. Importantly, ligand-receptor analysis suggested that maternal cold stress exposure disrupts neurodevelopmental programs through altered cell-cell signalling within Cycling NSPCs predominantly in females. These findings demonstrate that prenatal maternal cold stress exposure drives sex-specific effects on fetal neurodevelopment and uncover distinct cellular pathways that may contribute to sex differences seen in the presentation and risk of many NDDs.

  单细胞扰动筛选
• Spatially resolved heterogeneity of lymphatic vasculature in the adult lung
  GSE325297Mus musculus2 个样本2026-10-29

  Background. Lung lymphatic drainage of interstitial fluid is essential for preventing pulmonary edema, a condition characterized by the accumulation of extravascular fluid that impedes respiratory gas exchange and can be fatal. Beyond fluid regulation, lung lymphatics also serve as conduits for immune cell trafficking, supporting both surveillance and mounting of host immune responses during lung infection. Despite their essential roles, the cellular and functional heterogeneity of lung lymphatic endothelial cells (LECs) remains poorly defined. Methods. Leveraging single nucleus sequencing technology, we investigated LEC heterogeneity in the homeostatic adult mouse lung. Results. We identified Stabilin-2 (Stab2), a Class H scavenger receptor, as a unique marker of a distinct subset of LECs in lymphatic vessels adjacent to pulmonary veins and in alveolar regions. A separate distinct subset of LECs is defined by expression of Polycystic Kidney and Hepatic Disease 1-Like-1 (Pkhd1l1), a component of stereocilia, and these lymphatic vessels are localized to the bronchovascular bundle. Conclusions. Our findings suggest that lung LECs are not a uniform population but instead compromise molecularly distinct and spatially organized lymphatic vessels, possibly with specialized functions. These results lay the groundwork for further studies geared towards understanding the roles of cellular origin in lung LEC heterogeneity, whether lymphatics in other organs have analogous spatial organization, and whether these disparate cells and vessels have functional differences in fluid homeostasis and immune regulation during pulmonary disease pathogenesis.

  单细胞空间转录组
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons [scRNA-Seq]
  GSE317781Mus musculus2 个样本2026-10-29

  The transcriptional and epigenetic mechanisms that govern neuronal subtype differentiation and diversification remain poorly defined, with auditory neurons among the least understood. Here, we investigate the role of the proneural factor NEUROD1 using a delayed, self terminating conditional knockout (Neurod1ST) mouse model that bypasses the early neuronal loss observed in germline mutants. By integrating NEUROD1 chromatin binding and histone profiling at E11.5 with transcriptomic analyses at E11.5, E14.5, and E18.5, we show that NEUROD1 is essential for coordinating the timing of neuronal differentiation. Neurod1 deletion prolongs progenitor-like states while prematurely accelerating differentiation and axonogenesis programs, reflecting the collapse of NEUROD1-dependent transcriptional networks and recruitment of compensatory pathways. NEUROD1 preferentially binds enhancers of neuronal differentiation genes and promotes their transition to active chromatin states, consistent with a pioneer factor function. Loss of Neurod1 disrupts these epigenomic transitions, alters neuronal migration and innervation trajectories, and ultimately leads to neuronal instability and apoptosis. During spiral ganglion neuron diversification, Neurod1ST neurons prematurely activate maturation markers and fail to generate Type Ic, instead adopting a Type Ib-like identity. These findings establish NEUROD1 as a central regulator that synchronizes differentiation, stabilizes neuronal identity, and shapes auditory neuron subtype diversity in the developing inner ear

  单细胞
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons [snRNA-Seq]
  GSE315741Mus musculus2 个样本2026-10-29

  The transcriptional and epigenetic mechanisms that govern neuronal subtype differentiation and diversification remain poorly defined, with auditory neurons among the least understood. Here, we investigate the role of the proneural factor NEUROD1 using a delayed, self terminating conditional knockout (Neurod1ST) mouse model that bypasses the early neuronal loss observed in germline mutants. By integrating NEUROD1 chromatin binding and histone profiling at E11.5 with transcriptomic analyses at E11.5, E14.5, and E18.5, we show that NEUROD1 is essential for coordinating the timing of neuronal differentiation. Neurod1 deletion prolongs progenitor-like states while prematurely accelerating differentiation and axonogenesis programs, reflecting the collapse of NEUROD1-dependent transcriptional networks and recruitment of compensatory pathways. NEUROD1 preferentially binds enhancers of neuronal differentiation genes and promotes their transition to active chromatin states, consistent with a pioneer factor function. Loss of Neurod1 disrupts these epigenomic transitions, alters neuronal migration and innervation trajectories, and ultimately leads to neuronal instability and apoptosis. During spiral ganglion neuron diversification, Neurod1ST neurons prematurely activate maturation markers and fail to generate Type Ic, instead adopting a Type Ib-like identity. These findings establish NEUROD1 as a central regulator that synchronizes differentiation, stabilizes neuronal identity, and shapes auditory neuron subtype diversity in the developing inner ear

  单细胞
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons [scRNAseq_E115]
  GSE315597Mus musculus2 个样本2026-10-29

  The transcriptional and epigenetic mechanisms that govern neuronal subtype differentiation and diversification remain poorly defined, with auditory neurons among the least understood. Here, we investigate the role of the proneural factor NEUROD1 using a delayed, self terminating conditional knockout (Neurod1ST) mouse model that bypasses the early neuronal loss observed in germline mutants. By integrating NEUROD1 chromatin binding and histone profiling at E11.5 with transcriptomic analyses at E11.5, E14.5, and E18.5, we show that NEUROD1 is essential for coordinating the timing of neuronal differentiation. Neurod1 deletion prolongs progenitor-like states while prematurely accelerating differentiation and axonogenesis programs, reflecting the collapse of NEUROD1-dependent transcriptional networks and recruitment of compensatory pathways. NEUROD1 preferentially binds enhancers of neuronal differentiation genes and promotes their transition to active chromatin states, consistent with a pioneer factor function. Loss of Neurod1 disrupts these epigenomic transitions, alters neuronal migration and innervation trajectories, and ultimately leads to neuronal instability and apoptosis. During spiral ganglion neuron diversification, Neurod1ST neurons prematurely activate maturation markers and fail to generate Type Ic, instead adopting a Type Ib-like identity. These findings establish NEUROD1 as a central regulator that synchronizes differentiation, stabilizes neuronal identity, and shapes auditory neuron subtype diversity in the developing inner ear

  单细胞
• Long-read sequencing reveals transcriptome diversity in the development
  GSE352002Mus musculus3 个样本2026-10-28

  The thymus is recognized as one of the most pivotal endocrine and immune organs within the human body. This study investigated the thymus transcriptome using PacBio single-molecule long-read sequencing technology, addressing the limitations of current transcriptome analyses. By sequencing mouse thymus tissue at critical postnatal developmental stages (7 days, 4 weeks, and 4 months), we performed the first long-read full-length isoform survey of postnatal mouse thymus development. A total of 136,104 transcripts were identified and mapped to 16,667 annotated genes and 22,465 previously unannotated transcript loci. Comparative analysis across the three datasets revealed differences in transcript composition, alternative splicing patterns, and fusion transcript detection. These comparisons provide a descriptive overview of transcriptome diversity across postnatal developmental stages, while the biological mechanisms underlying these differences require further investigation. Selected exon skipping events and RNA fusion events were experimentally validated. In addition, more long non-coding RNAs were characterized, offering new perspectives on the regulatory networks underlying immune function and development. In summary, PacBio long-read sequencing provides a valuable resource for characterizing full-length transcript isoforms and transcriptome complexity in the postnatal mouse thymus.
• Transcriptomic Analysis Identifies Candidate Molecular Mechanisms Underlying SCF+G-CSF-Reduced Neuropathology in Aged APP/PS1 Mice
  GSE345694Mus musculus8 个样本2026-10-28

  Alzheimer’s disease (AD) is characterized by amyloid pathology, neuroinflammation, and cognitive decline. Our previous studies demonstrated that combined treatment with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) reduces AD pathology in APP/PS1 mice. In this study, we performed transcriptomic analysis to investigate candidate molecular mechanisms underlying the effects of SCF+G-CSF in aged APP/PS1 mice. Aged APP/PS1 mice received daily subcutaneous injections of SCF+G-CSF or vehicle for 12 days, and age-matched wild-type mice served as controls. Gene-chip analysis identified 27 differentially expressed genes in SCF+G-CSF-treated versus vehicle-treated APP/PS1 mice and 89 differentially expressed genes in APP/PS1 versus wild-type mice. The findings identify treatment-associated transcriptional changes involving immune regulation, metal ion homeostasis, and other molecular pathways potentially relevant to AD pathology.
• Real-world river water organic pollutant mixture induces ovarian hyperandrogenism via aryl hydrocarbon receptor activation
  GSE343592Mus musculus9 个样本2026-10-28

  Humans are exposed to complex mixtures of endocrine-disrupting chemicals (EDCs) in the real world. Most prior studies, however, focus on individual EDCs. Here, we investigated the ovarian impact of organic pollutant mixtures extracted from the Raritan River, a heavily industrialized watershed in central New Jersey, using a three-dimensional (3D) in vitro ovarian follicle culture system. Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) identified organic pollutant mixtures dominated by alkylphenols, pharmaceuticals, per- and polyfluoroalkyl substances (PFAS), and phthalates, together with previous reports demonstrating that the Raritan River also contains hydrophobic persistent organic pollutants (POPs), including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and dioxins. In vitro exposure to the Raritan River-derived EDC mixture did not affect follicle growth and ovulation but dose-dependently increased preovulatory testosterone secretion while suppressing postovulatory progesterone production. Transcriptomic analysis, Gene set enrichment analysis (GSEA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and in situ RNA hybridization revealed widespread reprogramming of follicular somatic cell gene expression, including altered steroidogenic pathways and activation of aryl hydrocarbon receptor (AhR) signaling. An established AhR agonist, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), reproduced the phenotype of EDC mixture-induced hyperandrogenism, which was reversed by a selective AhR inhibitor. Together, this study demonstrates that real-world EDC mixtures, particularly AhR-activating chemicals, disrupt ovarian steroidogenesis and induce hyperandrogenism, highlighting EDC mixtures as an underrecognized mechanism linking aquatic pollution to impaired women’s reproductive health.
• Glutamine Metabolism as a Rheostat of CD4+ T cell Pathogenic Function in Metabolic Dysfunction-Associated Steatotic Liver Disease
  GSE341871Mus musculus7 个样本2026-10-28

  Metabolic dysfunction-associated steatotic liver disease (MASLD) severity is independently linked with pathogenic CD4+ T cell responses and skewed hepatic glutamine (Gln) metabolism. Whether these processes interact to drive disease progression remains unclear. Here, we identify hepatic Gln depletion as a key feature of steatohepatitis that is linked with increased hepatic CD4+ T cell inflammation and hepatocellular damage in humans. In complementary mouse models, both total hepatic and hepatic CD4+ T cell Gln levels were similarly reduced. Restoration of hepatic Gln through supplementation selectively restrained hepatic CD4+ T cell inflammatory programs and alleviated hepatocellular damage and disease severity. Mechanistically, T cell-intrinsic Gls1-mediated glutaminolysis limited O-GlcNAcylation to dampen pathogenic CD4+ T cell inflammation. Importantly, Gln treatment dampened CD4+ T cell-mediated injury in human liver organoids. Together, these findings establish hepatic CD4+ T cell-intrinsic Gln metabolism as a critical rheostat of pathogenic inflammation in MASLD and invoke metabolism-targeted strategies to restrict disease progression.
• Immune landscape and intercellular crosstalk in the cornea of an autoimmune-mediated dry eye disease
  GSE333335Mus musculus2 个样本2026-10-28

  We have employed a single cell sequencing approach using 10x genomis scRNAseq to study the immune composition in autoimmune induced dry eye cornea. This study found a diverse immune cell composition, including T cells, B cells, neutrophils and macrophages. Moreover, we characterized cell signaling communication networks between immune and epithelial and stormal cells.

  单细胞
• The Circadian Clock controls Hepatic Inflammation in Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) [Multi-omics]
  GSE327440Mus musculus6 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.

  多组学
• Med1 Deletion Reprograms Dental Epithelium into Primitive Hair-Forming Epidermal Architecture via Trp63 Driven Epigenetic Alterations
  GSE316847Mus musculus1 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
• Soundwave Priming Enhances the Therapeutic Efficacy of Mesenchymal Stromal Cell–Derived Extracellular Vesicles in Acute Respiratory Distress Syndrome
  GSE316041Mus musculus8 个样本2026-10-28

  Our findings provide a robust model in which the UC-EVs cargo modulated by pFUS priming drives improved mitochondrial energetics, barrier protection, and resolution of inflammation, supporting the translational potential of pUC-EVs.
• Alternative splicing plays an important role in fast chemical reprogramming [scRNA-Seq]
  GSE292990Mus musculus2 个样本2026-10-28

  To investigate the role of Ptbp3 during reprogramming, scRNA-seq was carried out with RNAs isolated from the reprogramming intermediates transfected with shNC or shPtbp3.

  单细胞
• Alternative splicing plays an important role in fast chemical reprogramming [RNA-Seq]
  GSE292989Mus musculus4 个样本2026-10-28

  To investigate the role of Ptbp3 during reprogramming, deep RNA-seq was carried out with RNAs isolated from the reprogramming intermediates transfected with shNC or shPtbp3.
• OMP38 of carbapenem-resistant Acinetobacter baumannii-mediated mtDNA release activates the cGAS-STING signalling to induce inflammatory response
  GSE280491Mus musculus5 个样本2026-10-28

  Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a major threat in the treatment of bacterial infection, and immunotherapy in a non-antibiotic-dependent manner is an effective way to overcome CRAB infection. However, the role of the innate immune response in CRAB infection is poorly understood. Here, we reported that CRAB infection induced a cytosolic DNA-sensing signalling pathway and significant IFN-β production in mice post CRAB infection. The knockout of STING reduced bacterial burden, the production of inflammatory cytokines and lung injury in mice post CRAB infection. The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and the adaptor protein stimulator of interferon genes (STING) were required for CRAB-induced IFN-β expression in macrophages. Intriguingly, CRAB utilized outer membrane vesicles (OMVs) to transport outer membrane protein 38 (OMP38) into mitochondria, triggering mitochondrial DNA (mtDNA) release into the cytosol through the mitochondrial permeability transition pore (mPTP) and activating the cGAS-STING signalling. Finally, epigallocatechin gallate (EGCG) was demonstrated to block the activation of the cGAS-STING pathway and ameliorate CRAB-induced excessive inflammatory response. These results demonstrated that the early innate immune response to CRAB infection was activated in a cGAS-STING-dependent manner, which could be a potential therapeutic target for CRAB infection.
• Filamin B, a novel RNA-binding protein, extensively regulates the expression and alternative splicing of genes associated with osteoblast development in MC3T3-E1 cells
  GSE246668Mus musculus6 个样本2026-10-28

  Filamin B (FLNB) encodes an actin-binding protein and also acts as a novel RNA-binding protein involved in cell movement and signal transduction, playing a crucial role in bone growth. However, the impact of dysregulated FLNB expression on the molecular level in the skeletal system remain unknown. In this study, stably transfected MC3T3-E1 cell lines with FLNB knockdown were constructed to investigate the regulatory mode of FLNB in the molecular level of osteoblasts by RNA-seq sequencing. Functionality experiments revealed that FLNB knockdown led to decreased proliferation, migration, and differentiation of MC3T3-E1 cells compared to the empty vector group. In addition, differentially expressed genes (DEGs) and results showed that FLNB was mainly enriched in the expression of genes related to osteoblast proliferation, differentiation and migration, such as ITGA10, Cebpβ, Grem1, etc. Alternative splicing (AS) results observed significant changes in Tpx2 and Evc related to skeletal development.According to the current study, we conducted the first investigation into the transcriptomic and alternative splicing level of FLNB in pre-osteoblast to analyze its regulatory function in bone growth and development. This study lays the foundation for the current insights into the mechanisms of gene regulation mediated by FLNB during skeletal development.
• SB89: A Murine Dermis-Derived Macrophage Cell Line for Studies of Skin Immune Responses
  GSE351881Mus musculus6 个样本2026-10-27

  Resident dermal macrophages (DMs) play essential roles in maintaining skin homeostasis and initiating inflammatory responses during tissue injury and against infectious agents. However, studies of their cellular mechanisms have been limited by their low abundance in steady-state skin and by technical challenges in isolating resident DMs. Here, we describe the generation and characterization of a novel DM cell line, termed SB89. F4/80+ skin-resident DMs were sorted and immortalized using J2 retroviral transduction. SB89 cells display a stable, homogeneous macrophage phenotype and distinct surface markers compared with Langerhans cells and alveolar macrophages. Functionally, SB89 cells efficiently phagocytose methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, zymosan particles, and apoptotic cells, and effectively kill MRSA. Importantly, SB89 cells respond to LPS, as evidenced by production of IL-6, TNF, and Nos2, and by MRSA-induced production of inflammatory cytokines, chemokines, and eicosanoids. Importantly, SB89 cells are genetically tractable and amenable to genetic manipulation, supporting efficient miRNA gene silencing via RNAi and gene introduction via plasmid-based gene expression transfection. Bulk RNA-seq analysis revealed that SB89 cells are transcriptionally distinct from immortalized bone marrow-derived macrophages and are enriched for pathways associated with innate immune responses, chemotaxis, cell adhesion, and GPCR signaling. Together, these findings establish SB89 as a renewable, genetically tractable dermis-derived macrophage model that can support reproducible studies of skin-associated macrophage functions. This cell line represents a powerful platform for mechanistic, genetic, and translational studies in skin immunobiology.