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。

• Longitudinal spatial mapping of tumor–immune microenvironment following electrochemotherapy of cutaneous melanoma metastases
  GSE352662Homo sapiens16 个样本2026-10-31

  Background: Electrochemotherapy (ECT) utilizes reversible electroporation for localized chemotherapeutic delivery, where beyond local cytotoxicity, ECT acts as an in situ immunomodulator. However, the dynamic spatial orchestration of the TME that translates this localized therapy into potential abscopal-like responses in untreated lesions remains poorly understood. Methods: To uncover the mechanisms of evolving tumor microenvironment (TME) that dictate this immune activation, we applied Xenium spatial transcriptomics to longitudinally sampled in-transit cutaneous melanoma metastases from three patients, capturing baseline immune states and two distinct post-ECT intervals (two-to-three and nine-to-ten days). Furthermore, to explicitly characterize potential abscopal-like effects, biopsies were collected also from non-treated lesions. Following sample integration, we annotated cell types and identified functional subpopulations of key compartments, which we compared across treatment timepoints and patients. Further, we resolved functional spatial niches and identified spatially localized immune front, which we characterized and linked to patients' clinical responses. Results: Our analysis uncovered heterogeneous patient trajectories: a robust local and regional responder, a localized-only responder, and a delayed regional responder. These divergent outcomes were linked to baseline TME heterogeneity that was reflected by diverging proportions of functional spatial niches. While the partial responder exhibited an immune-cold architecture, complete responders were characterized by an immune-permissive TME with a prominent immune front at the interface of malignant and immune-active niches. Molecular profiling of these spatial boundaries exposed patient-specific signatures of activation and suppression within infiltrating T cells, myeloid cells, and fibroblasts. Although the states of malignant cells remained predominantly unchanged in the partial responder, the malignant cells of complete responders transitioned into a unique SOX2-OT-expressing dormant state, sequestered within keratinocyte-rich zones and characterized by an immunosuppressive signature post-treatment. Conclusions: Together, our findings suggest that beside local ablation, ECT might actively instigate regional antitumor immunity, a therapeutic effect that we observed in two patients harboring a permissive TME. Further, our deep spatial TME profiling identifies several exploratory observations on the effects of ECT that should be addressed in future studies.

  空间转录组
• Cooperative interaction of Foxp3 and STAT5 confers regulatory T cell fitness by tuning IL-2-induced gene expression [ATAC-Seq]
  GSE352613Mus musculus32 个样本2026-10-31

  Transcription factor Foxp3, with its singular role in differentiation and function of regulatory T (Treg) cells in physiologic and inflammatory settings, is thought to act by modulating transcriptional responses to activatory extracellular cues including pro-inflammatory cytokines. However, the underlying mechanisms remain largely unknown. After Foxp3 is induced during Treg differentiation upon STAT5 activation downstream of interleukin-2 receptor (IL-2R), sustained STAT5 signaling facilitates fitness and suppressive capacity of mature Treg cells. We found that Foxp3 and phospho-STAT5 (pSTAT5) form a stable transcriptional complex. Upon IL-2 sensing, Foxp3 is recruited in a pSTAT5-dependent manner to GAS-motif-enriched cis-regulatory elements that are developmentally primed by STAT5 in Treg precursors prior to Foxp3 expression. Using chemogenetically and pharmacologically induced protein degradation, we demonstrate that Foxp3 modulates STAT5 signaling in activated Treg cells to selectively modulate their transcriptional response to IL-2, most prominently involving a Myc-dependent gene module. Our studies suggest that direct Foxp3-STAT5 cooperativity fine-tunes STAT5 signaling downstream of IL-2 receptor activation to support functionality of differentiated Treg cells.
• Integrated transcriptomic and tissue profiling reveals imprinted-gene dysregulation and PEG10 upregulation in liposarcoma
  GSE352573Homo sapiens42 个样本2026-10-31

  Liposarcoma is a rare cancer, comprising four major histological subtypes with distinct molecular features and limited therapeutic options in advanced disease. We investigated subtype-associated transcriptional programmes, imprinted-gene dysregulation and the expression context of PEG10 in liposarcoma. Bulk RNA sequencing was performed on 16 independent liposarcoma tumours and five adjacent non-tumour tissues. PEG10 was further examined by RT-qPCR, RNA fluorescence in situ hybridisation (RNA-FISH), exploratory TCGA-SARC survival analysis and an external single-cell RNA-sequencing dataset of dedifferentiated liposarcoma. Transcriptomic profiling identified subtype-associated programmes and significant enrichment of imprinted genes in liposarcoma. PEG10 showed tumour-associated upregulation supported by RT-qPCR and RNA-FISH. PEG10 was detectable across all major subtypes, with the highest bulk transcript levels in myxoid liposarcoma, while RNA-FISH signal was higher in G3 than G2 tumours. In TCGA-SARC, higher PEG10 expression was associated with shorter overall survival, whereas DDLPS-specific analyses were not significant. External single-cell data localised PEG10 predominantly to tumour and cycling-cell populations and to angiogenesis- and invasion-associated tumour-cell states. Histological subtype accounted for a substantial component of PEG10-associated pathway variation. These findings identify PEG10 as a tumour-associated imprinted transcript in liposarcoma and provide a framework for further investigation of its biological and clinical relevance in larger, subtype-balanced cohorts.

  单细胞
• Circulating microRNA profiles in patients with MASLD-related cirrhosis and hepatic encephalopathy: an exploratory pilot study
  GSE352557Homo sapiens14 个样本2026-10-31

  Background and Aims: Hepatic encephalopathy (HE) is a common complication of cirrhosis, characterized by biochemical alterations in the central nervous system microenvironment. Although the molecular mechanisms underlying HE have been partly characterized at the protein level, their upstream regulation remains poorly understood. This study aimed to characterize circulating microRNA (miRNA) expression in patients with overt HE and identify the biological pathways associated. Materials and methods: Ten patients with MASLD-related cirrhosis and HE and four controls – subjects without chronic liver disease – attending the Liver Unit of the University Hospital of Messina, were enrolled after the exclusion of neurological comorbidities. Blood samples were collected at enrolment, cell-free RNA was isolated from plasma using the miRNeasy Kit, and functional enrichment analysis was performed using DIANA-miRPath v4. Results: Compared with controls, patients with HE showed downregulation of miR-18a and upregulation of miR-150, miR-214, miR-296, miR-320, miR-423-5p, miR-483-5p, miR-484, miR-486, miR-636, miR-92a, miR-10b, miR-1233, miR-1255b, miR-1285, miR-1290, miR-1291, miR-30a-5p, miR-338-5p, and miR-378. Functional enrichment analysis identified pathways and molecular functions related to glycolipid metabolism regulators and neuronal homeostasis signalling. Conclusion: Study results reveal a complex miRNA-associated network involving metabolic dysfunction, neuroinflammation, cellular integrity, and neuronal plasticity, highlighting the biological complexity of MASLD-related cirrhosis with HE. Keywords: Metabolic dysfunction-associated steatotic liver disease, liver cirrhosis, hepatic encephalopathy, microRNAs.
• Analysis of Sacituzumab Govitecan-Resistant Syngeneic Patient-Derived Xenograft Pairs
  GSE352548Homo sapiens18 个样本2026-10-31

  This study identifies RNA expression changes in models that have acquired Sacituzumab Govitecan (SG) resistance over extended treatment in triple-negative breast cancer patient-derived xenograft (PDX) models. Patients diagnosed with triple-negative breast cancer do not have many targeted treatment options, yet SG has recently been approved for first-line treatment of these patients. SG is an antibody drug conjugate that binds to TROP2 and delivers a topoisomerase 1 inhibitor, SN-38, as its payload. We have selected three PDX models which were initially sensitive to SG treatment, and treated them with suboptimal doses of SG until the tumors grew through treatment. Previous studies have shown that resistance to SG could be due to inefficient antibody internalization or lack of payload efficacy, however, other genetic or transcriptomic factors may influence drug sensitivity. We hypothesize that individual acquired SG resistance mechanisms will uncover features that can be targeted to extend the duration of response to SG.
• Gut microbial equol production associates with cognitive trajectories and suppresses NLRP3 inflammasome activation
  GSE352509Mus musculus12 个样本2026-10-31

  Many intestinal microbiome-produced metabolites have neuroimmunomodulatory properties. To identify metabolites associated with cognition and neuroinflammation, we measured microbially derived metabolites in the blood serum of 1,206 cognitively normal participants from the Wisconsin Alzheimer’s Disease Research Center (ADRC) and the Wisconsin Registry for Alzheimer’s Prevention (WRAP). We found that serum presence of equol, a microbially-produced metabolite derived from the soy-isoflavone daidzein, was related to preclinical cognition over time in a sex-dependent manner, suggesting that microbe-derived equol may attenuate cognitive decline through sex-specific biological pathways. Additionally, serum equol was associated with slower accumulation of the CSF biomarkers GFAP, S100B, and NfL, suggesting equol may be linked to glial regulation and neuronal integrity. To understand how equol may mediate inflammation systemically to reduce neuroinflammation, we performed bulk RNA-sequencing on bone marrow-derived macrophages (BMDMs) and found S-equol treatment modestly altered pathways associated with the NOD, LRR, and pyrin domain containing (NLRP3) inflammasome, an established driver of neuroinflammation in Alzheimer’s disease. We used ELISAs and caspase-1 immunoblots to show S-equol inhibits NLRP3 activation in BMDMs, evidenced by significantly decreased IL-1β secretion and caspase-1 processing after equol treatment. We confirmed that this effect is directly dependent on equol’s inhibition of potassium efflux. These findings lay a strong foundation for future studies examining the neuroimmunomodulatory action of equol in NLRP3 driven disease and cognitive decline.
• Targeting the Alk4 pathway protects against age-related bone loss.
  GSE352343Mus musculus15 个样本2026-10-31

  Osteoporosis is a chronic age-related condition where imbalanced activities between bone-forming osteoblasts and bone-resorbing osteoclasts result in the progressive loss of bone volume and reduced bone quality. While drugs that target osteoclast activity have been developed, there remains a lack of efficient therapies that increase osteoblast function in aging bones. Here, we showed that in mouse femurs, levels of Activin signaling progressively increased with age and strongly correlated with the loss of trabecular bone. When we removed Alk4, the type I receptor for Activin in osteoblast progenitors, Alk4 cKO mice had increased numbers of osteoblasts, an increased rate of bone formation, and increased trabecular bone acquisition. These results indicate that Activin through Alk4 signaling inhibits bone formation and osteoblast activity and is likely associated with osteoporosis. Furthermore, when we injected 2-year-old male mice with Alk4-Fc to capture circulating Activin, aged mice were protected against loss of trabecular bone in both femurs and L5 vertebrae. Remarkably, Alk4-Fc also prevented the age-related decrease in muscle mass that normally accompanies age-related bone loss, indicating that circulating Activins also play a role in sarcopenia. In summary, our preclinical mouse models reveal that circulating Activins play a primary role in age-related bone and muscle loss and can be efficiently targeted to alleviate osteoporosis and sarcopenia in aging mice.
• Proteasomes in extracellular vesicles mediate most transcriptional effects in recipient colorectal cancer cells
  GSE351755Homo sapiens28 个样本2026-10-31

  Extracellular vesicles (EVs) transmit lipids, proteins and RNA between cells of the organism. Among their cargo, EVs contain different forms of proteasomes - multi-subunit protein complexes responsible for degradation of most intracellular proteins. The transmission of proteasomes by EVs from one cell to another has been recently shown; however the biological significance of the phenomenon is generally unknown. Here we purified EVs from control colorectal adenocarcinoma cells and cells treated with IFN-γ, a cytokine known to activate expression of specific proteasome forms - non-constitutive proteasomes (ncPs). The obtained vesicles were incubated with two different irreversible proteasome inhibitors: carfilzomib and ONX-0914, targeting all forms and specifically ncPs, correspondingly. EVs were then incubated with control or carfilzomib-treated colorectal adenocarcinoma cells and the cellular RNA was obtained, followed by transcriptome acquisition and analysis. Incubation of control and carfilzomib-treated cells with treated or non-treated EVs obtained from control donor cells induced almost no effect on gene expression in recipient cells. However, vesicles obtained from IFN-γ-treated cells modulated expression of 53 genes in control cells and 2 genes in carfilzomib-treated cells. Treatment of vesicles with either one or another proteasome inhibitor affected the expression of 49 genes in control cells. In carfilzomib-treated cells inhibition of proteasomes in EVs affected 21 genes. Importantly, in both cases inhibition of ncPs in vesicles using ONX-0914 induced more pronounced effects on transcription in recipient cells. Most of the genes with differential expression were involved in oxidative phosphorylation. Obtained results indicate that most of the effects mediated in recipient cells by EVs were associated with the activity of proteasomes and specifically non-constitutive proteasomes, highlighting novel insights into EVs mediated proteasome transfer.
• Parallel transcriptomics reveals insect developmental shifts and gall-associated host transcriptional differences in Quadrastichus erythrinae and Erythrina variegata
  GSE351178Erythrina variegata; Quadrastichus erythrinae12 个样本2026-10-31

  Gall development involves changes in insect development and host tissue gene expression. This study used separate RNA-seq comparisons of Quadrastichus erythrinae larvae and pupae and of galled and ungalled Erythrina variegata petioles collected from one host tree during one sampling occasion. Insect reads were analyzed against a reference genome, while plant reads were assembled de novo and analyzed using a frozen sequence-provenance exclusion mask. Differential expression and annotation-based candidate analyses were used to describe developmental-stage differences in the insect and gall-associated transcriptional differences in the host. The comparisons support candidate functional themes for further investigation and do not directly test molecular interactions between the organisms.
• Tidal ventilation induces divergent repair responses in lung epithelial cells and fibroblasts mediated by IL-6 signaling
  GSE350588Homo sapiens24 个样本2026-10-31

  Mechanical ventilation may alter lung repair by differentially regulating epithelial and fibroblast responses. This study investigated transcriptional responses in human bronchial epithelial cells (BEAS-2B) and lung fibroblasts (MRC-5) exposed to bronchoalveolar lavage fluid from patients receiving tidal mechanical ventilation or continuous positive airway pressure (CPAP). Following scratch injury, cells were cultured with bronchoalveolar lavage fluid, with or without the IL-6 receptor inhibitor tocilizumab, and profiled using the Ion AmpliSeq Transcriptome Human Gene Expression Panel on an Ion S5 Prime sequencer. Differential gene expression and pathway analyses identified distinct responses associated with ventilatory condition, including altered inflammatory signaling and epithelial repair programs in BEAS-2B cells and increased extracellular matrix remodeling and profibrotic signaling in MRC-5 fibroblasts. IL-6 receptor blockade attenuated ventilation-associated transcriptional differences in both cell types. These data support a role for IL-6 signaling in the divergent epithelial and fibroblast repair responses associated with mechanical ventilation.
• SARS-CoV-2 Nsp2 reprograms host immunity to drive pathogenic inflammation
  GSE350427Mus musculus; Severe acute respiratory syndrome coronavirus 236 个样本2026-10-31

  Despite the end of the COVID-19 pandemic, SARS-CoV-2 continues to circulate endemically, highlighting the need to better understand the viral determinants of pathogenesis. Putative functions of the non-structural protein 2 (Nsp2) have been studied in vitro but how Nsp2 affects pathogenesis and overall viral fitness in vivo has yet to be demonstrated. Here, we generated a recombinant SARS-CoV-2 lacking Nsp2 (ΔNsp2) to investigate its role in viral replication and disease. While ΔNsp2 replicated comparably to wild-type virus in vitro and in vivo, its deletion resulted in markedly attenuated disease in K18-hACE2 mice. Wild-type virus infection induced a strong pro-inflammatory response associated with increased recruitment of monocytes and macrophages, whereas ΔNsp2 virus infection promoted a more balanced antiviral response characterized by enhanced lymphocyte and NK cell recruitment. This was accompanied by reduced pulmonary and systemic inflammation and distinct transcriptional programs, including downregulation of pathways related to RNA processing and translation. Mechanistically, CLIP-seq and proximity labeling suggest that Nsp2 interacts with host RNA and components of the translational machinery. Together, our findings identify Nsp2 as a key virulence factor that drives immunopathology by skewing host immune responses, highlighting its role as a regulator of host–pathogen interactions.
• RNA-seq of mouse bone marrow mesenchymal stem cells treated with different NPY concentrations
  GSE349627Mus musculus12 个样本2026-10-31

  Mouse bone marrow mesenchymal stem cells (BMSCs) were treated with neuropeptide Y (NPY) at 0, 1e-8, 1e-7, or 1e-6 mM for 7 or 14 days. Twenty-four polyA UID-mRNA-seq paired-end libraries (three biological replicates per treatment and time point) were sequenced to assess transcriptomic changes associated with low versus high NPY intervention.
• PERSIST-On enables heritable and fine-tunable human gene activation [RNA-seq]
  GSE348876Homo sapiens15 个样本2026-10-31

  PERSIST-On uses CRISPR prime editing to insert an endogenous transcription-factor binding motif (ELF2X) into target gene promoters, driving heritable, fine-tunable gene activation with only transient editor expression. To assess transcriptome-wide effects and specificity of ELF2X insertion, we performed mRNA-seq on cells with ELF2X inserted into the EPCAM, HER2, or IL2RA promoter and on matched non-targeting editor controls.
• Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams [PIP-Seq]
  GSE348705Mus musculus16 个样本2026-10-31

  How memory consolidates via DNA methylation mechanisms during sleep in the basolateral amygdala (BLA), a critical brain region for fear memory, remains unknown. We performed whole-genome bisulfite sequencing (WGBS) on fear conditioning (FC)-activated cells from the BLAs of adult male mice experiencing either sleep or sleep deprivation following FC learning, evaluated at Day 7 and Day 28 timepoints. Additionally, Day 7 samples include paired single-nucleus RNA sequencing (snRNA-seq) using PIPseq technology. This dataset enables the integration of multi-omics (methylome and transcriptome) to understand learning-induced epigenomic programming in the BLA.

  单细胞多组学
• Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams
  GSE348542Mus musculus16 个样本2026-10-31

  How memory consolidates via DNA methylation mechanisms during sleep in the basolateral amygdala (BLA), a critical brain region for fear memory, remains unknown. Here, we performed whole-genome bisulfite sequencing (WGBS) on fear conditioning (FC)-activated cells from the BLAs of adult male mice experiencing sleep or sleep deprivation following FC learning, at a week (day 7) and a month (day 28) timepoints. This dataset enables the investigation of cytosine methylation changes (CG and non-CG contexts) associated with learning-induced epigenomic programming in the BLA.
• Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams [batch 1 WGBS]
  GSE348488Mus musculus12 个样本2026-10-31

  How memory consolidates via DNA methylation mechanisms during sleep in the basolateral amygdala (BLA), a critical brain region for fear memory, remains unknown. Here, we performed whole-genome bisulfite sequencing (WGBS) on fear conditioning (FC)-activated cells from the BLAs of adult male mice experiencing sleep or sleep deprivation following FC learning, at a week (day 7) and a month (day 28) timepoints. This dataset enables the investigation of cytosine methylation changes (CG and non-CG contexts) associated with learning-induced epigenomic programming in the BLA.
• Sleep-dependent DNA methylation remodeling in basolateral amygdala fear engrams [batch 2 WGBS]
  GSE348480Mus musculus16 个样本2026-10-31

  How memory consolidates via DNA methylation mechanisms during sleep in the basolateral amygdala (BLA), a critical brain region for fear memory, remains unknown. Here, we performed whole-genome bisulfite sequencing (WGBS) on fear conditioning (FC)-activated cells from the BLAs of adult male mice experiencing sleep or sleep deprivation following FC learning, at a week (day 7) and a month (day 28) timepoints. This dataset enables the investigation of cytosine methylation changes (CG and non-CG contexts) associated with learning-induced epigenomic programming in the BLA.
• Pericytes modulate brain vascular integrity in social stress in mice and human depression [cultured cells RNA-Seq]
  GSE348103Homo sapiens27 个样本2026-10-31

  Major depressive disorder (MDD) is a leading cause of disease burden with low therapeutic efficacy. Chronic social stress, MDD’s main risk factor, is associated with neurovascular pathology in mood-regulating brain regions. Pericytes ensheathe endothelial cells and modulate blood-brain barrier (BBB) functions, but contribution of these mural cells to stress responses or psychiatric conditions is unknown. Here, we show sex-specific transcriptomic, morphological and functional alterations in pericytes in the prefrontal cortex (PFC) following stress exposure in female mice and women with MDD. Endothelial cell-to-pericyte crosstalk via PDGFB:PDGFRB signaling is important for BBB dynamics. Reduction of Pdgfrb+ pericyte coverage in the PFC induces anxiety- and depression-like behaviours in female, but not male mice, while viral-mediated increased pericyte-endothelial communication promotes stress coping. RNA-seq of human endothelial cells and pericytes exposed to MDD serum reveals changes in extracellular matrix-related genes and cell-cell communication. PDGF-BB serum level correlates with depressive symptoms and diagnosis. Altogether, our findings shed light on a mechanism underlying PFC dysfunction in MDD, a therapeutic target and blood biomarker. Our work provides tools to manipulate pericytes applicable for vascular, neurodegenerative, or inflammatory diseases all characterized by high rates of depression.
• Functional landscape of enhancers that control the blood-brain barrier
  GSE347657Mus musculus21 个样本2026-10-31

  Cis-regulatory elements (CREs) that control of the blood-brain barrier (BBB) transcriptional program have been studied by transducing candidate CREs together with a GFP reporter into mouse brain endothelial cells (ECs) in vivo using recombinant Adeno-Associated Viruses (rAAVs). Approximately one-quarter of DNA segments encompassing regions of accessible chromatin (ATACseq peaks) in or near 16 genes that are highly expressed in CNS ECs confer brain EC gene expression when transduced using rAAVs. For six active CREs, site-directed mutagenesis showed that ERG/ETS and LEF/TCF motifs are consistently important for CRE activity, while FOX and ZIC motifs are variably important for CRE activity. Transcription factor (TF) occupancy maps, determined by the CUT&RUN method for ERG, LEF1, KLF4, and ZIC3 in and near the same 16 genes in acutely isolated mouse brain ECs, showed that one or more of these TFs occupied binding sites in nearly all of the 55 candidate CREs, with a modestly higher occupancy level among the 14 candidate CREs that were active in vivo in the rAAV assay compared to the 41 candidate CREs that were inactive in vivo in the rAAV assay. As observed previously for ERG and LEF1 (Li et al., 2026), chromatin occupancy by KLF4 and ZIC3 is highly enriched in open chromatin that is brain EC-specific, regions that represent the strongest candidates for brain EC-specific CREs. These studies provide foundational information for research aimed at generating endothelial cells with BBB properties in vitro.
• Pericytes modulate brain vascular integrity in social stress in mice and human depression
  GSE347183Mus musculus10 个样本2026-10-31

  Major depressive disorder (MDD) is a leading cause of disease burden with low therapeutic efficacy. Chronic social stress, MDD’s main risk factor, is associated with neurovascular pathology in mood-regulating brain regions. Pericytes ensheathe endothelial cells and modulate blood-brain barrier (BBB) functions, but contribution of these mural cells to stress responses or psychiatric conditions is unknown. Here, we show sex-specific transcriptomic, morphological and functional alterations in pericytes in the prefrontal cortex (PFC) following stress exposure in female mice and women with MDD. Endothelial cell-to-pericyte crosstalk via PDGFB:PDGFRB signaling is important for BBB dynamics. Reduction of Pdgfrb+ pericyte coverage in the PFC induces anxiety- and depression-like behaviours in female, but not male mice, while viral-mediated increased pericyte-endothelial communication promotes stress coping. RNA-seq of human endothelial cells and pericytes exposed to MDD serum reveals changes in extracellular matrix-related genes and cell-cell communication. PDGF-BB serum level correlates with depressive symptoms and diagnosis. Altogether, our findings shed light on a mechanism underlying PFC dysfunction in MDD, a therapeutic target and blood biomarker. Our work provides tools to manipulate pericytes applicable for vascular, neurodegenerative, or inflammatory diseases all characterized by high rates of depression.
• GR signaling impairs osteoblast differentiation via Map7d2
  GSE346858Mus musculus14 个样本2026-10-31

  The glucocorticoid receptor (GR) is an important regulator of skeletal homeostasis; however, the molecular mechanisms through which it regulates osteogenic differentiation remain incompletely understood. Here, we investigated the role of GR using two complementary primary murine osteogenic cell models, bone marrow stromal cells (BMSCs) and bone-derived primary osteoblasts (pOs), together with comparative transcriptomic analyses. RNA sequencing (RNAseq) revealed extensive transcriptional changes following GR knockdown. Despite substantial differences in gene expression profiles of the two osteogenic cell models, pathway enrichment analyses revealed common biological processes, including MAPK signaling and cell migration. Comparative transcriptomic analysis further identified only 17 genes that were consistently regulated in the same direction in both cell preparations, among which Map7d2 emerged as a previously unrecognized GR-responsive candidate. Co-depletion of Map7d2 partially rescued the impairment of osteogenic differentiation caused by GR depletion.Taken together, our study reveals common molecular responses to GR depletion across two primary murine osteogenic cell models and provides new insights into the transcriptional and signaling networks underlying GR-regulated osteogenic differentiation.
• Transcription directs the migration of meiotic recombination intermediates
  GSE346163Saccharomyces cerevisiae SK113 个样本2026-10-31

  During meiosis, genetic diversity arises from the resolution of branched DNA intermediates called Holliday junctions to create crossovers—sites of reciprocal exchange between parental chromosomes. Holliday junctions arise during the repair of Spo11-induced DNA breaks, yet the principles linking break formation, repair, and chromosome architecture remain unclear. Top3, a type IA topoisomerase, acts on Holliday junction-containing recombination intermediates, but its spatiotemporal dynamics are unknown. Here, we map Top3 catalytic activity throughout meiotic prophase with strand specificity and nucleotide resolution. We identify a DNA sequence motif associated with catalysis and a pattern of activity around Spo11 hotspots that requires ongoing repair and Top3’s helicase partner, Sgs1. Strikingly, Top3 activity shifts over time, influenced by transcription, cohesin, and the crossover factors Msh5 and Mer3, redistributing toward sites of convergent transcription—known locations of enhanced meiotic cohesin association. Upon prophase exit, as crossovers are resolved, Top3 activity subsides. Remarkably, maps of genome-wide recombination reveal that crossover frequency is elevated at these same regions of convergent transcription. Collectively, we propose that Top3 tracks the transcription-directed migration of Holliday junction-containing meiotic recombination intermediates from Spo11 hotspots towards cohesin-associated axis sites, where crossover resolution occurs, promoting accurate meiotic chromosome segregation.
• Tissue Nano-Transfection Promotes Vascularization to Enhance Acellular Nerve Allograft–Mediated Nerve Repair
  GSE344504Mus musculus16 个样本2026-10-31

  Peripheral nerves possess an inherent capacity for regeneration, yet functional recovery following an injury remains inconsistent despite advances in microsurgical repair. Autologous nerve grafts are the gold standard for complex peripheral nerve injuries (PNI) but are constrained by limited donor availability, donor-site morbidity, and size mismatches. Acellular nerve allografts (ANAs) offer off-the-shelf availability and can bridge longer defects, but their performance is hindered by the lack of intrinsic Schwann cells and vascular structures, essential for axonal regeneration. Here, we report on the use of Tissue Nanotransfection (TNT), a novel non-viral platform that allows the delivery of nucleic acids into solid tissues in combination with ANAs. We used TNT to reprogram resident nerve cells toward a vasculogenic phenotype to locally increase vascularization and improve outcomes following PNI reconstruction. We show that vasculogenic transcription factors (Etv2, Fli1, and Foxc2; EFF) drive transcriptomic changes in vitro. In vivo, vasculogenic TNT increases the number of endothelial cells within ANAs as early as 5 weeks post-treatment. Mice receiving ANAs combined with vasculogenic TNT exhibited superior functional recovery, including enhanced muscle strength and progressive restoration outperforming ANAs only controls. Region-specific transcriptomics reveal that the site of the TNT application along the host nerve critically influences the regenerative response. Together, these findings identify vasculogenic TNT as a potent, non-viral strategy to enhance ANA-mediated repair by promoting localized vasculogenesis and supporting improved functional recovery and muscle protection.
• RNA‑seq analysis of leaf transcriptomes in wild‑type and slzf3 mutant tomato under normal and cold temperatures.
  GSE342135Solanum lycopersicum12 个样本2026-10-31

  SlZF3, a C2H2‑type zinc finger protein, plays a pivotal role in tomato cold tolerance. To elucidate the underlying molecular mechanisms and identify its potential target genes under cold stress, we performed transcriptome profiling of wild‑type and slzf3 mutant leaves under normal and low‑temperature conditions. Integrated multi‑omics analysis enabled the identification of downstream target genes involved in SlZF3‑regulated metabolic pathways, providing a comprehensive view of the SlZF3‑mediated cold regulatory network.
• Paternal methylphenidate exposure alters sperm miRNAs and induces intergenerational behavioral and transcriptional changes that are largely reversed by washout
  GSE341541Mus musculus12 个样本2026-10-31

  To determine whether paternal methylphenidate exposure alters sperm small noncoding RNA profiles and whether these changes are reversible after drug withdrawal, male BALB/c mice were administered methylphenidate (15 mg/kg) or saline (10 mL/kg) for 28 days. Cauda epididymal sperm were collected immediately after treatment or after a 40-day washout period and analyzed by small RNA sequencing.
• NLRP3 inflammasome-mediated pyroptosis exacerbates insulin resistance upon exposure to nanoplastics with different surface chemistries
  GSE338308Danio rerio15 个样本2026-10-31

  The surface chemical properties of nanoplastics (NPs), such as surface charge and functional groups, can markedly influence their toxicological effects. Recent studies have shown that NPs can disrupt glucose homeostasis. However, under metabolically susceptible conditions, such as hyperglycemia and metabolic dysfunction, differences in metabolic toxicity and the underlying mechanisms among surface-modified NPs remain unclea
• Targeting ERO1α Triggers Tumor Immunosurveillance in Triple-Negative Breast Cancer
  GSE337796Mus musculus24 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Targeting ERO1α Triggers Tumor Immunosurveillance in Triple-Negative Breast Cancer [RNA-seq]
  GSE337795Mus musculus12 个样本2026-10-31

  Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited responsiveness to immune checkpoint blockade. Here, we identify endoplasmic reticulum oxidoreductase 1 alpha, a key regulator of oxidative protein folding, as a determinant of tumor immunogenicity and immunotherapy response in TNBC. Unbiased proteomic profiling demonstrated that ERO1α deficiency remodels the TNBC glycoproteome, leading to enrichment of pathways associated with innate immune signaling. Although ERO1α loss did not affect tumor cell growth, it reshaped the immune tumor microenvironment, enhancing antigen presentation, altering myeloid-cell composition, and modulating PD-1/PD-L1–associated signaling. Functionally, ERO1α deficiency sensitized otherwise refractory TNBC tumors to PD-1 blockade, resulting in durable tumor regression in immunocompetent hosts. In contrast, ERO1α deletion in bone marrow–derived immune cells had minimal effects on tumor growth or therapeutic response, supporting an ERO1α tumor-intrinsic mechanism. Pharmacologic inhibition of ERO1α with the novel small-molecule inhibitor I29 phenocopied ERO1α genetic deletion and enhanced the efficacy of anti–PD-1 therapy. Together, these findings identify ERO1α-dependent glycoproteome remodeling as a regulator of antitumor immunity and a therapeutically actionable mechanism of immune checkpoint responsiveness in TNBC.
• Targeting ERO1α Triggers Tumor Immunosurveillance in Triple-Negative Breast Cancer [scRNA-seq]
  GSE336881Mus musculus12 个样本2026-10-31

  Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited responsiveness to immune checkpoint blockade. Here, we identify endoplasmic reticulum oxidoreductase 1 alpha, a key regulator of oxidative protein folding, as a determinant of tumor immunogenicity and immunotherapy response in TNBC. Unbiased proteomic profiling demonstrated that ERO1α deficiency remodels the TNBC glycoproteome, leading to enrichment of pathways associated with innate immune signaling. Although ERO1α loss did not affect tumor cell growth, it reshaped the immune tumor microenvironment, enhancing antigen presentation, altering myeloid-cell composition, and modulating PD-1/PD-L1–associated signaling. Functionally, ERO1α deficiency sensitized otherwise refractory TNBC tumors to PD-1 blockade, resulting in durable tumor regression in immunocompetent hosts. In contrast, ERO1α deletion in bone marrow–derived immune cells had minimal effects on tumor growth or therapeutic response, supporting an ERO1α tumor-intrinsic mechanism. Pharmacologic inhibition of ERO1α with the novel small-molecule inhibitor I29 phenocopied ERO1α genetic deletion and enhanced the efficacy of anti–PD-1 therapy. Together, these findings identify ERO1α-dependent glycoproteome remodeling as a regulator of antitumor immunity and a therapeutically actionable mechanism of immune checkpoint responsiveness in TNBC.

  单细胞
• MicroRNA annotations from the parasitic plant Cuscuta saururi
  GSE335728Cuscuta saururi14 个样本2026-10-31

  The Cuscuta genus of parasitic plants is widespread and can impact agricultural productivity. Previous studies of C. campestris have described the existence of a special type of microRNA that functions to enter host tissues and regulate host mRNAs. These "interface-induced" microRNAs are uniquely transcribed by RNA polymerase III, have a common promoter element, and specifically accumulate in haustorial tissues of the parasite. Here, we investigate the existence of such "interface-induced" microRNAs in a second Cuscuta species, C. saururi. C. saururi is a recently resurrected species that forms part of the C. gronovii species complex. We used a highly contiguous genome assembly of C. saururi, along with small RNA-seq, to annotate both the interface-induced and canonical microRNA genes of C. saururi.