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。

• Epigenomic analysis of the myometrium during late implantation revealed regulatory elements in genes related to the cellular zinc homeostasis pathway in pigs (RNA-Seq)
  GSE246432Sus scrofa12 个样本2026-10-30

  The myometrium, composed of the inner circular muscle (CM) and outer longitudinal muscle (LM), is crucial in establishing and maintaining early pregnancy. However, the molecular mechanisms involved are not well understood. In this study, we identified the transcriptomic features of the CM and LM collected from the mesometrial (M) and anti-mesometrial (AM) sides of the pig uterus on day 18 of pregnancy during the placentation initiation phase. Some genes in the cellular zinc ion level regulatory pathways (MT-1A, MT-1D, MT-2B, SLC30A2, and SLC39A2) were spatially and highly enriched in uterine CM at the mesometrial side. In addition, the histone modification profiles of H3K27ac and H3K4me3 in uterine CM and LM collected from the mesometrial side were characterized. Genomic regions associated with the expression of genes regulating the cellular zinc ion level were detected. Moreover, six highly linked variants in the H3K27ac-enriched region of the pig SLC30A2 gene were identified and found to be significantly associated with the total number born at the second parity (P < 0.05). In conclusion, the genes in the pathways of cellular zinc homeostasis and their regulatory elements identified have implications for pig reproduction trait improvement and warrant further investigations.

  空间转录组
• H3K27me3 and total H3 ChIP-seq in stage 9, 11, and 12 Drosophila melanogaster embryos
  GSE352458Drosophila melanogaster12 个样本2026-10-29

  In an associated manuscript, we measured by ChIP-seq the genome-wide distribution of Histone H3 trimethylated at Lysine 27 (H3K27me3) and total Histone H3 in Drosophila embryos at three developmental stages following the maternal-to-zygotic transition: stage 9 (~NC14 + 2h), stage 11 (~NC14 + 4h), and stage 12 (~NC14 + 6h). These measurements extend a prior time course of H3K27me3 establishment during nuclear cycle 14 (NC14; GSE299311) and show that, after H3K27me3 appears local to Polycomb Response Elements (PREs) in mid-NC14, the modification continues to spread outward from these nucleation sites over the following ~6 hours. In the associated manuscript, these data are used to quantify the in vivo rate of H3K27me3 spreading and to benchmark a reaction-diffusion model of de novo Polycomb domain establishment by PRC2.
• Trisomy 21 Perturbs Oligodendrocyte Developmental States and Oligo-Neuron Communication in Human Forebrain Assembloids
  GSE352389Homo sapiens12 个样本2026-10-29

  Intellectual disability is a hallmark of Down syndrome (DS), caused by the triplication of human chromosome 21. Abnormal neuronal connectivity and impaired myelination are consistently observed in DS, yet the underlying mechanisms remain poorly understood. Here, we used DS-derived isogenic induced pluripotent stem cell-derived forebrain assembloids (FAs) to investigate oligodendrocyte lineage cell (OLLC) development and neuron-glia interactions. Trisomic FAs exhibited an expansion of BCAS1+ pre-myelinating OLLCs, without a corresponding increase in myelin basic protein (MBP) expression. Transcriptomic analyses identified a euploid-enriched, trophic and maturation-supportive state (OLLC_2-TMS) and a trisomy-enriched state, characterized by enhanced neuronal interactions and restricted progression beyond the pre-myelinating stage (OLLC_3-NID). These transcriptional signatures were also present in OLLCs from early postnatal human cortex. Increased excitatory neuronal contacts with pre-myelinating OLLCs accompanied ultrastructural myelin abnormalities in trisomic assembloids. Our findings suggest that trisomy redirects OLLC development toward a pre-myelinating state, uncoupling oligodendrocyte differentiation from productive myelination.

  扰动筛选
• 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.
• Cancer-Associated Transcriptional Readthrough Reveals Distinct Stress- and Proliferation-Related Programs
  GSE349075Homo sapiens47 个样本2026-10-29

  Transcriptional readthrough generates downstream-of-gene (DoG) RNAs through transcription beyond canonical termination sites. Although DoGs have been implicated in cellular stress and cancer, their biological and clinical significance remains poorly understood. We analyzed DoG transcripts in 787 experimental and 3,066 public RNA-seq profiles encompassing colorectal, lung, pancreatic, stomach, and thyroid cancers. RNA-seq library design strongly influenced DoG detection, with rRNA-depleted and paired-end libraries providing greater sensitivity than poly(A)-selected and single-end approaches. DoG abundance and expression were increased in most cancer types, whereas DoG length was largely unchanged. Joint analysis of DoG and parental gene expression identified two distinct classes of cancer-associated readthrough. DoGs upregulated independently of parental genes, consistent with dysregulated transcription termination, included 31 transcripts recurrently increased across all five cancer types and were associated with stress-related functions. In contrast, DoGs co-upregulated with their parental genes were enriched for proliferation-related processes. In an experimental cohort of 95 lung cancer patients receiving PD-(L)1 immune checkpoint therapy, higher abundance and expression of recurrent DoG signatures were associated with shorter progression-free survival (HR 2.53–3.24). These findings reveal distinct biological components of cancer-associated transcriptional readthrough and identify recurrent DoG signatures as candidate prognostic biomarkers.
• 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
• Multi-omics analysis reveals an EXOSC10-lncRNA-dependent checkpoint in nucleolar proteostasis recovery
  GSE329077Homo sapiens12 个样本2026-10-29

  Proteotoxic stress induced by heat shock drives the formation of nucleolar aggresomes. However, the mechanisms governing their resolution during recovery remain poorly understood. Here, we combine temporal quantitative proteomics, transcriptomics and live imaging to define the dynamics of the detergent-insoluble fraction during heat shock and recovery. We find that nucleolar aggresome recovery follows a multiphasic lag–burst–resolution kinetic program that tightly couples the recruitment of protein quality-control factors and remobilization of ribosomal proteins. We identify stress-induced long non-coding RNA IGS16 as a critical regulator of this process. IGS16 accumulates in the nucleolus upon heat shock where it restrains chaperone engagement. Clearance of IGS16 by the nucleolar exonuclease EXOSC10 is required to initiate nucleolar remodeling and enable HSP70-dependent restoration of ribosomal protein mobility. Notably, IGS16 degradation occurs independently of HSP70 ATPase activity, indicating that RNA turnover precedes and licenses chaperone-mediated aggregate resolution. Together, our findings uncover an RNA-dependent regulatory checkpoint that coordinates RNA metabolism and protein quality control to regulate nucleolar proteostasis recovery. This work also reveals a previously unknown function for EXOSC10 in stress-induced condensate dynamics control potentially through long non-coding RNA degradation.

  多组学
• AP-1 Family Member Transcription Factors Play a Critical Role in Human Beta Cell Replication and Differentiation
  GSE327169Homo sapiens21 个样本2026-10-29

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• 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 [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
  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
• 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.

  扰动筛选
• Non-canonical RNA binding of the MYBL2 transcription factor promotes melanoma (RNA-seq)
  GSE284544Homo sapiens12 个样本2026-10-29

  Melanoma originates from melanocytes, and the process of melanocyte malignant transformation is affected by various factors, including non-mutational gene alterations. MYBL2 is a transcription factor primarily known for its role in regulating cell cycle progression. In this study, we characterized that MYBL2 gain or amplification occurs in one fifth of the melanoma patients, and the aberrantly upregulated MYBL2 promotes melanoma growth while representing a melanoma vulnerability. Notably, MYBL2 can also binds RNA, and its oncogenic effect is mediated through its RNA binding function. Crosslinking-immunoprecipitation followed by high-throughput sequencing revealed that MYBL2 primarily binds protein-coding genes and introns. Interestingly, MYBL2 does not affect the RNA metabolism of its direct targets. Instead, its RNA binding function influences its association with chromatin and thereby rewiring the transcription program favoring poor patient survival. Surprisingly, we observed that MYBL2 binds RNA exclusively in melanoma cells, but not in melanocytes. This phenomenon is primarily due to the altered RNA background developed following melanoma transformation, while alternations within MYBL2 itself also involved in a lesser extent. Therefore, our work identified a novel oncogenic function of MYBL2 through its RNA binding activity, extending our current understanding of MYBL2 and highlighting a critical mechanism in melanoma progression.
• TFIIIC regulates SMC complex binding and 3D DNA contacts between tRNA genes [RNA-seq]
  GSE352551Caenorhabditis elegans15 个样本2026-10-28

  Transcription factor IIIC (TFIIIC) is a multi-subunit protein complex that recruits RNA polymerase III (Pol III) to the majority of its target genes. Evolutionarily conserved overlap between TFIIIC binding sites and the structural maintenance of chromosomes (SMC) complexes suggested a role for TFIIIC in SMC regulation and 3D organization of eukaryotic genomes; but the evidence has remained largely correlational due to the essential role of TFIIIC in recruiting RNA Pol III for transcription initiation. Here, we directly tested the function of TFIIIC in SMC complex regulation by using auxin inducible protein degradation in C. elegans. We performed Hi-C, ChIP-seq and mRNA-seq analyses upon acute depletion of TFTC-3, an essential TFIIIC subunit, and RPC-1, the catalytic subunit of RNA Pol III. Our results showed that TFIIIC is required for cohesin and condensin complexes binding to tRNA genes. TFIIIC is also required for increasing 3D contacts between distant tRNA genes located on the same or different chromosomes. Depletion of individual SMC complexes did not significantly reduce the tRNA gene contacts, suggesting redundancy or an independent mechanism mediating these contacts. Together, our study supports an RNA Pol III independent function for TFIIIC in regulating multiple SMC complexes, as well as the 3D organization of tRNA genes.
• 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.
• The analysis of mRNA and miRNA clarified the immune regulation mechanism of rainbow trout ( Oncorhynchus mykiss ) head kidney under IHNV infection
  GSE352277Oncorhynchus mykiss12 个样本2026-10-28

  The head kidney is a multifunctional organ that integrates hematopoiesis, antigen processing, immune signal transduction, antibody production and endocrine regulation to maintain the immune homeostasis of fish and resist pathogens. Several studies indicate that AS can produce functionally diverse protein isoforms and has become a vital regulatory mechanism in fish antiviral innate immunity. However, the mechanism of AS in antiviral response of head kidney is still unclear in rainbow trout. Accordingly, this study analyzed AS events in the head kidney of rainbow trout though RNA-seq. This study provided a theoretical basis for the study of AS response mechanism of rainbow trout antiviral, and also provided potential molecular targets for in-depth understanding of fish interferon signal transduction.
• QUAIL-100 Induces Distinct, Multifunctional γδ T Cell Responses with Enhanced Durability Compared to Zoledronic Acid in Post-HSCT Pediatric Leukemia Patients
  GSE352026Homo sapiens21 个样本2026-10-28

  γδ T cells mediate potent anti-leukemic and anti-infective immunity following allogeneic hematopoietic stem cell transplantation (HSCT); however, standard Vγ9Vδ2 activation with zoledronic acid (ZOL) induces rapid terminal differentiation and functional exhaustion, limiting sustained therapeutic efficacy. Pathogen-driven γδ T cell responses, including those elicited by cytomegalovirus (CMV), exhibit greater functional diversity and durability, providing a conceptual framework for multimodal activation strategies. QUAIL-100, a quadruple-attenuated Listeria monocytogenes strain (Lm ΔactA/ΔinlB/ΔribC/ΔribF), was evaluated as a novel γδ T cell activator that engages combinatorial signals including phosphoantigens, pathogen-associated molecular patterns, and co-stimulatory pathways.
• 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.
• Tau A152T risk variant drives distinct cell type transcriptional signatures in AD and PSP
  GSE350921Homo sapiens28 个样本2026-10-28

  The A152T point mutation is a rare genetic variant in the tau gene (MAPT) that is linked to risk of Alzheimer’s disease (AD) and frontotemporal dementia spectrum disorders, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). To uncover mechanisms through which the A152T variant contributes to risk of tauopathy, we performed single-nucleus RNA sequencing (snRNA-seq) on postmortem brain tissue collected from A152T carriers and pathology-matched non-carriers with either AD or PSP, along with age-matched controls. These efforts revealed that despite similar cell type composition across groups, A152T carriers exhibited distinct cell type-specific transcriptional changes in both AD and PSP. Differential expression analysis identified excitatory neurons, oligodendrocytes and astrocytes as the most affected cell populations in AD and PSP, and these same cell types showed the strongest A152T-specific changes. These findings identify transcriptional alterations that differentiate sporadic AD and sporadic PSP from AD-A152T and PSP-A152T, as well as shared molecular signatures unique to A152T carriers in both PSP and AD. Donor-level pseudobulk analyses showed broad directional support with the single-nucleus findings, although the proportion of donor-supported genes varied across cell type and comparison. Importantly, merging sporadic and A152T cases into a single disease group was found to mask transcriptional differences in several cell types in both AD and PSP, indicating divergence in transcriptional signature and highlighting the importance of screening for genetic risk variants like A152T in snRNA-seq data from human cohorts.

  单细胞
• Bulk RNA-seq profiling of regulatory and effector T cells of C57BL/6 mice
  GSE350087Mus musculus12 个样本2026-10-28

  Regulatory T cells (Tregs) maintain immune tolerance, whereas effector T cells (Teffs) mediate immune responses. Imbalance between Tregs and Teffs may contribute to immune dysregulation in type 1 diabetes mellitus (T1DM). Here, we performed bulk RNA sequencing of splenic Tregs and Teffs from control and streptozotocin-induced diabetic C57BL/6 mice to characterize disease-associated transcriptional alterations. Tregs in T1DM exhibited enhanced proliferative, effector-associated, and metabolic transcriptional programs, alongside reduced expression of genes involved in immunoregulation, lineage maintenance, tissue homing, metabolic fitness, and stress adaptation. Meanwhile, Teffs adopted a hyperactivated, but functionally imbalanced transcriptional state characterized by enhanced proliferative and inflammatory programs alongside dysregulated metabolic, signaling, and migratory functions. This study identified transcriptional alterations of splenic Tregs and Teffs in control and STZ-induced diabetic C57BL/6 mice, providing candidate molecular markers for further investigation of T-cell dysregulation in T1DM.
• Paired Transcriptomic Profiling Identifies Shared Liver Metas-tasis-Associated Molecular Features in Colorectal Cancer
  GSE347316Homo sapiens12 个样本2026-10-28

  Colorectal cancer liver metastasis (CCLM) is closely associated with poor patient prognosis, yet patient-specific molecular heterogeneity complicates the identification of recurrent molecular changes during metastasis. To address this, we performed RNA sequencing on paired primary tumors and liver metastases synchronously resected from six patients and analyzed gene expression changes using a paired design that accounted for interpatient variability. This analysis identified differentially expressed genes (DEGs) and metastasis-associated pathways through functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). The reproducibility of these changes was further assessed across multiple independent publicly available transcriptomic datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Selected candidate genes were additionally evaluated in a metastasis-selected colorectal cancer cell model, in which several genes showed expression changes consistent with the transcriptomic findings. Together, these results indicate that recurrent molecular changes accompany CCLM despite substantial interpatient heterogeneity and provide a strategy for identifying metastasis-associated molecular features and potential therapeutic targets

  细胞图谱
• Furan fatty acids reprogram hepatic lipid metabolism via acyl-CoA conjugates in obesity.
  GSE347256Mus musculus24 个样本2026-10-28

  Dietary fish oil (FO) and omega-3 fatty acids are associated with cardiometabolic benefits, yet their molecular mediators remain incompletely defined. Furan fatty acids (FuFAs), a distinct lipid class enriched in FO, have emerged as potential regulators of metabolic health. Here, we identify and quantify FuFA species in prescription omega-3 formulations and natural fish oils, and synthesize structurally engineered analogs designed to isolate antioxidant activity and β-oxidation susceptibility from FuFA bioactivity. In a diet-induced obesity mouse model, both natural and synthetic FuFAs reduced fat accumulation and inflammatory markers, while 11U3-2M additionally produce significant improvement in glucose tolerance, dyslipidemia, and hepatic steatosis. The superior activity of 11U3-2M reflects the stable accumulation of its acyl-CoA conjugate that activates peroxisome proliferator-activated receptor alpha (PPARα) signaling and allosterically inhibits acetyl-CoA carboxylases (ACCs) to reprogram hepatic lipid metabolism. These findings position FuFAs as functional dietary lipids contributing to fish oil’s metabolic effects and define fatty acid structural determinants that govern hepatic metabolic activity.
• Super-enhancer NR125945 drives prostate cancer malignancy via long-range chromatin interactions [RNA-Seq]
  GSE346320Homo sapiens12 个样本2026-10-28

  Genetic susceptibility plays an essential role in prostate cancer (PCa) risk, while the functional mechanisms underlying several classic risk loci remain largely uncharacterized. Here, we identified a PCa specific super-enhancer within 1q42.3 locus, termed NR125945-SE. Through comparative H3K27ac ChIP-seq analysis, we observed that NR125945-SE is highly active in PCa cells compared to normal controls. NR125945-SE contributes to PCa malignant progression. Mechanistically, integrative analysis combining RNA-seq and 4C-seq data revealed that NR125945-SE regulates the expression of CAPN2 and KRT19 through long-range chromatin interactions. Furthermore, we demonstrated that NR125945-SE activity is mediated by the cooperative binding of multiple transcription factors. In summary, our findings provide insights into a functional epigenetic element within a classic genetic risk locus, proposing a mechanism by which super-enhancer-mediated regulation promotes prostate cancer progression.
• Time-resolved RNA-seq reveals a phased transcriptional response to TGFβ stimulation
  GSE343789Mus musculus40 个样本2026-10-28

  Fibroblast differentiation into matrix-producing, contractile myofibroblasts is accompanied by metabolic reprogramming, but whether these changes precede differentiation or arise from the activated phenotype remains unclear. To define when transcriptional remodeling emerges after TGFβ stimulation, we performed bulk RNA-seq on cardiac fibroblasts treated with TGFβ or bFGF for 1, 6, 12, 24, or 48 h. Our transcripomics revealed only 394 genes were differentially expressed at 1 h, but 4,188 DEGs were detected by 6 h, with the total DEG burden peaking at 24 h. These findings support a phased, time-dependent remodeling of the cardiac fibroblast transcriptome in response to TGFβ relative to bFGF in which an initially limited response occurs at 1 h, expands substantially by 6 h, and subsequently encompasses cell cycle regulation, stress responses, developmental- and differentiation-associated programs, cell adhesion, and extracellular matrix remodeling.
• A High-Throughput Functional 3D Droplet Microfluidic Platform for Function-to-Transcriptome Profiling Identifies Candidate lncRNAs Associated with Engineered NK Cell Function
  GSE343647Homo sapiens12 个样本2026-10-28

  Background: Natural killer (NK) cell–based immunotherapies show considerable promise for cancer treatment; however, their efficacy against solid tumors remains limited by functional heterogeneity and the restrictive tumor microenvironment. Engineered NK cells, including mesothelin-directed chimeric antigen receptor cytokine- induced memory-like (MSLN-CAR CIML) NK cells, exhibit enhanced cytotoxic potential, yet the transcriptional programs underlying effective tumor killing remain poorly defined. Although protein-coding regulators of NK cell function have been extensively studied, the contribution of long non-coding RNAs (lncRNAs) to cytotoxic NK cell states remains largely unexplored, particularly in engineered NK cell therapies. Methods: To address this gap, we developed and applied a three-dimensional (3D) Matrigel-based droplet microfluidic screening platform that enables single-cell resolution analysis of NK–tumor interactions. Unlike conventional bulk transcriptomic approaches, this function-to-transcriptome workflow enables functional isolation of killer and non-killer NK-cell populations prior to transcriptomic profiling enabling the direct comparison of transcriptional programs associated with cytotoxic function while minimizing confounding effects of bulk population analyses. Using this approach, we profiled donor-matched MSLN-CAR CIML NK cells and CIML NK controls from three independent donors. Results: Comparative transcriptomic analysis revealed widespread differences in lncRNA expression between killer and non-killer NK cell populations, characterized predominantly by broad lncRNA downregulation that was consistently observed across donors and more pronounced in MSLN-CAR CIML NK cells than in CIML controls. Integrated lncRNA-mRNA analyses prioritized candidate lncRNA–gene pairs based on genomic proximity and coordinated co-expression patterns, identifying several lncRNAs associated with cytotoxic gene programs. These transcriptional signatures were further associated with enrichment of cytotoxic and inflammatory pathways characteristic of highly functional NK cell states. Conclusions: Together, these findings demonstrate the utility of our functional droplet microfluidic screening platform in prioritizing candidate lncRNAs associated with cytotoxic NK cell states within matrix-restricted tumor environments. By integrating functional phenotyping with transcriptomic profiling, this platform provides a framework for identifying candidate lncRNA and other potential biomarkers associated with cytotoxic NK states for future mechanistic validation and the rational optimization of NK cell–based immunotherapies for solid tumors.

  单细胞
• Real-world river water organic pollutant mixture induces ovarian hyperandrogenism via aryl hydrocarbon receptor activation [follicular]
  GSE343593Mus musculus10 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.
• Development and preclinical evaluation of a decoy DLL4-encoding oncolytic HSV-1 for solid tumors II
  GSE334567Mus musculus; Homo sapiens24 个样本2026-10-28

  Preclinical and clinical investigation of oncolytic HSV-1 (oHSV) treatment for cancer has indicated increased Notch signaling in tumors after treatment. Since Notch activation often heralds cancer cell stemness, angiogenesis, and invasion, the induction of this pathway after oHSV virotherapy can support tumor growth and limit response to virotherapy. Here, we evaluated the impact of blocking DLL4, a Notch ligand, on virotherapy. Matched tumor biopsies pre- and post-oHSV (CAN-3110, NCT03152318) treatment revealed an induction of DLL4 post-therapy. We observed that expression of a recombinant soluble decoy DLL4 (sDLL4) could block Notch activation in tumor cells. Thus, we engineered an oHSV vector designed to encode for soluble DLL4 (OVsDLL4) to block DLL4-mediated signaling. RNA sequencing and gene set enrichment analysis revealed that, relative to control oHSV, OVsDLL4 blocked Notch and sprouting angiogenesis pathways after treatment. Despite slower virus replication in vitro, OVsDLL4 cytotoxicity remained effective against tumor cells. Transcriptome profiling also indicated a significant dysregulation of metabolic pathways related to oxidative phosphorylation and glutathione metabolism, in accordance with increased oxygen consumption observed by Seahorse analysis in cells expressing sDLL4. OVsDLL4-treated cells further showed increased reactive oxygen species relative to control oHSV-treated cells. Co-culture of infected tumor cells with macrophages revealed that OVsDLL4 treatment educated macrophage gene expression towards an inflammatory polarization. In vivo, the therapeutic efficacy of OVsDLL4 was underscored after treatment of mice bearing different solid tumors resulted in reduced tumor burden and prolonged survival.