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。

• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [2Cell_full_length_cDNA]
  GSE306936Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [mESC_RNAseq]
  GSE306934Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [KO_embryo_RNAseq]
  GSE306927Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• RHOX12L counteracts TRIM28-SETDB1 repression to activate embryonic IAP/MERVK retrotransposons [CUT&Tag]
  GSE306922Mus musculus样本未标注2026-10-30

  The onset of transcription in pre-implantation embryos includes the widespread transient activation of normally silenced endogenous retroviruses (ERVs) and other retrotransposons. In mice, DUX and OBOX transcription factors activate MERVL, but how other retrotransposons are activated remains largely unknown. Here, we identify RHOX12-like (RHOX12L) as a novel homeodomain-containing factor briefly activated by DUX in 2-cell embryos. Independent of specific DNA-binding activity, RHOX12L counteracts the general ERV repressor SETDB1 to transiently activate thousands of IAP/MERVK loci. Our biochemical studies reveal robust interaction of RHOX12L with SETDB1 as well as CBP/P300 and the BAF complex, concomitant with acetylation and chromatin opening at SETDB1-RHOX12L co-bound sites. In keeping, Rhox12l knockout embryos proved defective in IAP/MERVK activation. Furthermore, RHOX12L downregulates the OCT4 pluripotency network in embryonic stem cells (ESCs), potentially by sequestering OCT4 to de-repressed ERVs bearing upstream OCT4 binding sites. Taken together, we provide a mechanism for the strong, transient activation of the TRIM28/SETDB1-bound retrotransposon repertoire in pre-implantation embryos via co-activator tethering by RHOX12L.
• 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.
• LAMA2-related muscular dystrophy alters Schwann cell calcium homeostasis and increases peripheral nerve inflammation
  GSE351764Mus musculus43 个样本2026-10-29

  LAMA2-related muscular dystrophy (LAMA2-RD) affects skeletal muscle and peripheral nerves, yet the consequences of LAMA2 deficiency for peripheral nerve integrity beyond early postnatal development remain incompletely understood. We investigated sciatic nerve architecture and molecular alterations across postnatal life in hypomorphic Lama2dy2J/dy2J mice. LAMA2 localizes around the abaxonal surface of myelinating Schwann cells in control nerves. LAMA2-deficient nerves exhibited patchy regions lacking myelinated axons from early postnatal stages into adulthood, including expanded Remak bundles along with axons completely lacking normal Schwann cell ensheathment. In adult nerves, myelin infolding and reduced myelin circularity revealed abnormalities in the architecture of myelin that had formed. Bulk sciatic nerve RNA sequencing identified altered calcium-signaling and immune-related transcriptional signatures. Complementary Fura Red measurements in primary nerve-derived Schwann cell cultures demonstrated decreased intracellular calcium in LAMA2-deficient samples, while ATP-evoked responses were preserved. Older LAMA2-deficient nerves also exhibited increased CD45+CD11b+ myeloid-cell infiltration. Together, these observations extend the characterization of LAMA2-associated neuropathy into adulthood and identify calcium homeostasis and neuroimmune responses as candidate processes relevant to persistent peripheral nerve pathology.
• Mitochondrial Complex III Drives Skeletal Muscle Metabolic Reprogramming and Alters Glucose Utilization
  GSE347652Mus musculus12 个样本2026-10-29

  Mitochondrial dysfunction is closely associated with metabolic disease, yet how mitochondrial respiratory capacity influences skeletal muscle glucose handling remains poorly understood. Here, we investigate the role of mitochondrial Complex III in skeletal muscle using a muscle-specific Rieske iron-sulfur protein (RISP) knockout model. Loss of RISP did not impair basal Complex III respiratory capacity, but reduced skeletal muscle endurance while preserving muscle contractility and overall muscle structure. Importantly, Complex III deficiency was accompanied by alterations in systemic glucose metabolism. RISP-deficient mice exhibited lower basal glucose levels in fed and fasted states and improved glucose tolerance. Together, these findings suggest that impaired Complex III function triggers metabolic adaptations that extend beyond mitochondrial respiration and influence whole-body glucose handling. These findings identify mitochondrial Complex III as a potential metabolic checkpoint linking skeletal muscle oxidative capacity with glucose utilization and systemic glucose homeostasis. This work raises the possibility that enhancing skeletal muscle glucose utilization could represent a strategy to reduce glucose stress in metabolic disease, including diabetes.
• Lamin B1 physically regulates neuronal migration by modulating nuclear deformability in the developing cortex
  GSE347519Mus musculus18 个样本2026-10-29

  Neuronal migration positions billions of neurons to form a functional brain. Effective navigation through the cortex requires precise regulation of nuclear mechanics in migrating neurons. We demonstrate that Lamin B1 (LB1) regulates neuronal migration by modulating nuclear deformability. Elevated LB1 in neurons halted migration in vivo, without affecting laminar identity or pre-migratory gene expression. Mispositioned neurons subsequently caused electrophysiological defects in the brain. In vitro, increased LB1 raised nuclear stiffness, as measured by atomic force microscopy, and reduced neuronal motility in confined environments reconstituted with microchambers. Computational modeling predicted a temporal link between nuclear deformation and increased migration velocity, which was validated experimentally through live imaging. Notably, cerebral organoid assays using induced pluripotent stem cells established from patients with LMNB1 duplication exhibited impaired neuronal migration in a human model. Collectively, these findings establish LB1 as a critical regulator of nuclear mechanics, ensuring accurate spatiotemporal positioning of neurons.

  计算与 AI
• Acquired resistance to anti-PD-1 therapy is associated with tumor intrinsic macrophage reprogramming.
  GSE344292Mus musculus19 个样本2026-10-29

  Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis can produce durable tumor responses, but acquired resistance remains a major clinical problem. To define tumor-intrinsic transcriptional changes associated with acquired resistance, we generated independently derived anti-PD-1-resistant MC-38 colon adenocarcinoma cell lines (MC38-PR) by serial in vivo selection in immunocompetent C57BL/6 mice. Isotype-control-passaged MC38-ISO lines and the parental MC-38 line served as controls. Bulk RNA sequencing was performed to compare parental, isotype-control-passaged, and acquired anti-PD-1-resistant cell lines. These data support a multi-omic investigation of resistance in which independently derived resistant tumors converged on an immunosuppressive, macrophage-skewing tumor program despite retaining antigen-presentation machinery, interferon-gamma responsiveness, and most predicted neoantigens.

  多组学
• 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
• Smad4/SKI/SKIL-mediated repression of TGF-β signature is essential for a robust CD8 T cell response [viral vectors RNA-seq]
  GSE325275Mus musculus24 个样本2026-10-29

  Transforming growth factor-β (TGF-β) is an immunosuppressive cytokine that regulates both innate and adaptive immune responses. Earlier studies have shown that TGF-β plays a role in promoting T cell exhaustion during the later stages of chronic viral infection. In this study we examined the role of Smad4, a transcription factor downstream of TGF-β signaling, in regulating CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Surprisingly, we found that Smad4 acts as an intracellular repressor of TGF-β regulated genes during the early effector phase of the CD8 T cell response. Deletion of Smad4 in CD8 T cells resulted in a striking collapse of the virus-specific CD8 T cell response between day 5 to day 8 after LCMV clone 13 infection, with a 50–100-fold reduction in the number of LCMV-specific CD8 T cells at day 8. Both the stem-like and effector CD8 T cells generated in the absence of Smad4 have a dysregulated transcriptional and epigenetic program with elevated TGF-β signature. We show that Smad4 directly binds to several TGF-β target genes and other key genes involved in T cell survival and differentiation and regulates histone modifications and chromatin accessibility at these loci. Deletion of both TGF-β receptor II and Smad4 in antigen-specific CD8 T cells did not rescue the CD8 T cell response. This demonstrates that TGF-β target genes must be actively repressed by Smad4 intracellularly during the effector phase of the CD8 T cell response even in the absence of extracellular TGF-β signaling. By enforced expression of WT and mutant Smad4 in Smad4-KO CD8 T cells using retrovirus vectors, we show that the interaction between Smad4 and the TGF-β signaling repressors, SKI/SKIL, plays a critical role in antigen-specific CD8 T cells during the effector phase by turning off the TGF-β signature, whereas the interaction between Smad4 with TGF-β-induced phospho-Smad2/3 is dispensable at this stage. Consistent with this essential role of Smad4 during the effector phase, Smad4/SKI/SKIL interaction is also required for a robust CD8 T cell response against tumors and acute viral infection. Our findings documenting the striking requirement for Smad4-SKI-SKIL mediated restraint of TGF-β-associated program during the effector phase of the CD8 T cell response have implications for developing immunotherapeutic approaches against chronic viral infections and cancer.
• Smad4/SKI/SKIL-mediated repression of TGF-β signature is essential for a robust CD8 T cell response [kockout infection RNA-seq]
  GSE325274Mus musculus18 个样本2026-10-29

  Transforming growth factor-β (TGF-β) is an immunosuppressive cytokine that regulates both innate and adaptive immune responses. Earlier studies have shown that TGF-β plays a role in promoting T cell exhaustion during the later stages of chronic viral infection. In this study we examined the role of Smad4, a transcription factor downstream of TGF-β signaling, in regulating CD8 T cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection of mice. Surprisingly, we found that Smad4 acts as an intracellular repressor of TGF-β regulated genes during the early effector phase of the CD8 T cell response. Deletion of Smad4 in CD8 T cells resulted in a striking collapse of the virus-specific CD8 T cell response between day 5 to day 8 after LCMV clone 13 infection, with a 50–100-fold reduction in the number of LCMV-specific CD8 T cells at day 8. Both the stem-like and effector CD8 T cells generated in the absence of Smad4 have a dysregulated transcriptional and epigenetic program with elevated TGF-β signature. We show that Smad4 directly binds to several TGF-β target genes and other key genes involved in T cell survival and differentiation and regulates histone modifications and chromatin accessibility at these loci. Deletion of both TGF-β receptor II and Smad4 in antigen-specific CD8 T cells did not rescue the CD8 T cell response. This demonstrates that TGF-β target genes must be actively repressed by Smad4 intracellularly during the effector phase of the CD8 T cell response even in the absence of extracellular TGF-β signaling. By enforced expression of WT and mutant Smad4 in Smad4-KO CD8 T cells using retrovirus vectors, we show that the interaction between Smad4 and the TGF-β signaling repressors, SKI/SKIL, plays a critical role in antigen-specific CD8 T cells during the effector phase by turning off the TGF-β signature, whereas the interaction between Smad4 with TGF-β-induced phospho-Smad2/3 is dispensable at this stage. Consistent with this essential role of Smad4 during the effector phase, Smad4/SKI/SKIL interaction is also required for a robust CD8 T cell response against tumors and acute viral infection. Our findings documenting the striking requirement for Smad4-SKI-SKIL mediated restraint of TGF-β-associated program during the effector phase of the CD8 T cell response have implications for developing immunotherapeutic approaches against chronic viral infections and cancer.
• 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 [CUTTag_E115]
  GSE315627Mus musculus12 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
• 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
• Two-phase NEUROD1 pioneer activity regulates temporal differentiation and subtype specification of auditory neurons
  GSE315509Mus musculus12 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
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain
  GSE314268Mus musculus1,449 个样本2026-10-29

  This SuperSeries is composed of the SubSeries listed below.

  单细胞SuperSeries
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain [scRNA-seq]
  GSE314217Mus musculus491 个样本2026-10-29

  DNA methylation, particularly CpG methylation, plays a pivotal role in brain development, function, and aging. While recent single-cell brain methylome atlases have been mapped, they cannot distinguish between 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) due to their reliance on bisulfite conversion. This limitation is particularly problematic in the brain, where postmitotic neurons accumulate abundant 5hmCG, which may exert functions opposite to 5mCG. Consequently, how CpG modifications regulate neuronal gene expression remains incompletely understood. To address this, we present Joint-Cabernet, a bisulfite-free single-cell platform enabling simultaneous profiling of 5hmC, 5mC, and transcriptomes. Applying Joint-Cabernet to nuclei from adult mouse brains, we resolved cell-type-specific DNA hydroxymethylation landscapes, revealing elevated 5hmCG and 5hmCH levels in transcriptionally active genes and regulatory elements across diverse brain cell types and spatial gradients in cortical layers. This single-cell multi-omic atlas (DNA methylation, hydroxymethylation, and transcriptome) of the mouse brain provides a framework for studying methylation-driven regulation in the brain organization and neurodegenerative diseases.

  单细胞空间转录组细胞图谱多组学
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain [5mC]
  GSE314211Mus musculus479 个样本2026-10-29

  DNA methylation, particularly CpG methylation, plays a pivotal role in brain development, function, and aging. While recent single-cell brain methylome atlases have been mapped, they cannot distinguish between 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) due to their reliance on bisulfite conversion. This limitation is particularly problematic in the brain, where postmitotic neurons accumulate abundant 5hmCG, which may exert functions opposite to 5mCG. Consequently, how CpG modifications regulate neuronal gene expression remains incompletely understood. To address this, we present Joint-Cabernet, a bisulfite-free single-cell platform enabling simultaneous profiling of 5hmC, 5mC, and transcriptomes. Applying Joint-Cabernet to nuclei from adult mouse brains, we resolved cell-type-specific DNA hydroxymethylation landscapes, revealing elevated 5hmCG and 5hmCH levels in transcriptionally active genes and regulatory elements across diverse brain cell types and spatial gradients in cortical layers. This single-cell multi-omic atlas (DNA methylation, hydroxymethylation, and transcriptome) of the mouse brain provides a framework for studying methylation-driven regulation in the brain organization and neurodegenerative diseases.

  单细胞空间转录组细胞图谱多组学
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain [5hmC]
  GSE314195Mus musculus479 个样本2026-10-29

  DNA methylation, particularly CpG methylation, plays a pivotal role in brain development, function, and aging. While recent single-cell brain methylome atlases have been mapped, they cannot distinguish between 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) due to their reliance on bisulfite conversion. This limitation is particularly problematic in the brain, where postmitotic neurons accumulate abundant 5hmCG, which may exert functions opposite to 5mCG. Consequently, how CpG modifications regulate neuronal gene expression remains incompletely understood. To address this, we present Joint-Cabernet, a bisulfite-free single-cell platform enabling simultaneous profiling of 5hmC, 5mC, and transcriptomes. Applying Joint-Cabernet to nuclei from adult mouse brains, we resolved cell-type-specific DNA hydroxymethylation landscapes, revealing elevated 5hmCG and 5hmCH levels in transcriptionally active genes and regulatory elements across diverse brain cell types and spatial gradients in cortical layers. This single-cell multi-omic atlas (DNA methylation, hydroxymethylation, and transcriptome) of the mouse brain provides a framework for studying methylation-driven regulation in the brain organization and neurodegenerative diseases.

  单细胞空间转录组细胞图谱多组学
• Intestinal SAA1 and SAA2 regulate the balance between host inflammatory responses and metabolism
  GSE286869Mus musculus40 个样本2026-10-29

  Since their discovery as acute phase reactants, the SAA proteins have been an important focus of innate immunity research. Most SAA production is in the liver, and despite recent findings of their roles in promoting intestinal immunity, the precise functions of intestinal SAAs have not been well-studied. Validating and using an SAA1/2 double knock-out mouse, we found protective effects of SAA1 and SAA2 mitigating systemic and local inflammatory challenges, along with gene-, sex-, and location-specific responses to gut microbiota perturbations. SAA1 and SAA2 expression supports immunological protection in homeostasis but prioritizes metabolic activities under stress. From this work, we propose a new model in which SAA functions to regulate and integrate the interface between metabolism and host responses to inflammatory insults.

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• Lobe-specific liver transcriptional responses to portal vein ligation in wild-type and TNFR-knockout mice
  GSE352371Mus musculus22 个样本2026-10-28

  One-color mouse microarray expression profiles from untreated wild-type liver, ligated left and non-ligated right liver lobes after portal vein ligation, and an immediate postoperative sham reference. TNFR-knockout samples provide exploratory genotype comparisons.
• Drinking-Water 4,4'-Methylenedianiline Establishes a Longitudinally Tractable Mouse Model of Cholestatic Liver Injury
  GSE352312Mus musculus72 个样本2026-10-28

  This study examines time-dependent hepatic responses to 4,4'-methylenedianiline (MDA), a cholestatic hepatotoxicant, administered to male C57BL/6JJcl mice in drinking water. Liver RNA sequencing was performed in separate terminal cohorts sampled on Days 1, 2, 3, 4, and 8 after exposure to control tap water, thioacetamide (TAA; 300 mg/L), or MDA (750 mg/L). The dataset comprises 72 poly(A)-selected liver RNA-seq libraries and provides gene-level expression measurements for characterizing temporal transcriptional changes and comparing the MDA model with the TAA reference condition.
• 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.
• Sodium butyrate alleviates metabolic dysfunction-associated steatotic liver disease by activating PPAR-γ/FUNDC1‑mediated mitophagy to inhibit ferroptosis
  GSE351765Mus musculus18 个样本2026-10-28

  This study aims to elucidate the protective effects and underlying molecular mechanisms of sodium butyrate (NaB), a gut microbiota-derived metabolite, against metabolic dysfunction-associated steatotic liver disease (MASLD). Using high-fat diet (HFD)-fed mice and palmitic acid (PA)-treated hepatocytes, the study seeks to determine whether NaB alleviates hepatic steatosis and injury by restoring iron and redox homeostasis, upregulating glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1), and suppressing ferroptosis. It further aims to investigate whether these protective effects depend on FUN14 domain-containing protein 1 (FUNDC1)-mediated mitophagy, and to identify peroxisome proliferator-activated receptor gamma (PPAR-γ) as an upstream regulator of FUNDC1 expression and mitophagy. Collectively, this study aims to define a PPAR-γ/FUNDC1-mitophagy-ferroptosis axis through which NaB protects against MASLD, thereby linking a gut microbial metabolite to hepatic mitochondrial quality control and providing a potential therapeutic target and nutritional intervention strategy for MASLD.