GEO 数据集

主题由标题与摘要自动归类；样本量为数据集标注之和，SuperSeries 可能与其 SubSeries 重复计算。

• RNA-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.
• Gene expression in pericental and periportal hepatocytes
  GSE349461Mus musculus4 个样本2026-10-31

  Hepatic metabolic zonation enables periportal (PP) and pericentral (PC) hepatocytes to perform distinct metabolic functions. To characterize spatial differences in hepatic gene expression, we isolated PP and PC hepatocytes from mouse liver and performed RNA sequencing. This dataset provides transcriptomic profiles of PP and PC hepatocytes and enables identification of genes and pathways differentially regulated across the portal-to-central vein axis.

  空间转录组
• KLF16 and SIN3A facilitate endometrial cancer cell proliferation in association with CTD-2377D24.6
  GSE349296Homo sapiens6 个样本2026-10-31

  Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Pathogenetically, most cases arise from uncontrolled proliferative expansion of endometrial cells under prolonged estrogen stimulation, ultimately leading to malignant transformation within the glandular epithelium. Identifying key regulators of aberrant endometrial proliferation is therefore critical for developing novel therapeutic modalities against EC. In the present study, we characterized Kruppel-like factor 16 (KLF16), a transcription factor that drives proliferative signaling across multiple cellular components of the endometrium, including endothelial, epithelial, and smooth muscle cell types. Clinicopathological analysis revealed significantly elevated KLF16 expression in human EC tissues, which was positively associated with both advanced tumor stages and high histological grades. Genetic perturbation experiments demonstrated that knockdown of KLF16 robustly inhibited endometrial cancer cell proliferation in vitro and impeded tumor growth in vivo. Given its role as a master regulator controlling broad transcriptomic programs encompassing both protein-coding genes and non-coding RNAs, we performed unbiased screening and identified lncRNA CTD-2377D24.6 as a potential downstream mediator associated with KLF16 signaling. Notably, overexpression of CTD-2377D24.6 effectively counteracted the anti-proliferative effects induced by KLF16 depletion. Mechanistically, single-cell transcriptomics, coimmunoprecipitation, and functional assays demonstrated that SIN3A interacts with KLF16 and may contribute to the association between KLF16 and CTD-2377D24.6 expression, which is linked to enhanced endometrial cancer cell proliferation. Together, these findings established KLF16 contributes to endometrial cancer progression and highlight the KLF16/SIN3A/CTD-2377D24.6-associated regulatory axis as a potential molecular pathway relevant to EC proliferation.

  单细胞扰动筛选
• Targeting EGR1 Attenuates CCL2 Expression in Inflammatory Keratinocytes and Allergic Skin Inflammation
  GSE349203Homo sapiens5 个样本2026-10-31

  Early growth response 1 (EGR1) is a zinc-finger transcription factor involved in inflammatory gene regulation, but the extent to which pharmacological inhibition of EGR1 DNA-binding activity influences inflammatory transcriptional responses in keratinocytes remains incompletely understood. Here, we explored the transcriptional effects of pharmacological EGR1 inhibition in tumor necrosis factor-α (TNFα)-stimulated HaCaT keratinocytes. RNA sequencing was employed as an exploratory, hypothesis-generating screen using three structurally related EGR1 inhibitors (IT21, IT23, and IT25) to identify candidate genes showing concordant expression patterns across the three pharmacological perturbations. This analysis suggested broader changes in inflammation-associated transcriptional programs and identified several leukocyte-recruiting chemokines among the candidate genes. CCL2 was selected as a representative candidate for independent biological and mechanistic validation. IT25 treatment and EGR1 knockdown attenuated TNFα-induced CCL2 expression, while promoter-reporter analysis, EGR1-binding site mutagenesis, EGR1 overexpression, and chromatin immunoprecipitation supported EGR1-dependent transcriptional regulation of CCL2 in keratinocytes. Furthermore, topical IT25 treatment attenuated house dust mite-induced atopic dermatitis-like skin inflammation and was associated with reduced epidermal CCL2 expression and inflammatory cell infiltration in vivo. Collectively, these findings establish EGR1-dependent regulation of CCL2 in inflammatory keratinocytes and support further investigation of EGR1 DNA-binding activity as a pharmacological target in cutaneous inflammation.

  扰动筛选
• HNRNPH2-R114W remodels RNA splicing and neurodevelopmental gene programs in isogenic cerebral organoids
  GSE348913Homo sapiens4 个样本2026-10-31

  Autism spectrum disorder has been linked to disrupted RNA processing during corticogenesis, yet variant-specific mechanisms remain difficult to resolve. Isogenic cerebral organoids derived from a patient-derived induced pluripotent stem cell (iPSC) line carrying the HNRNPH2-R114W variant and its CRISPR-corrected counterpart serve as a human developmental model to investigate variant-associated RNA dysregulation. Imaging quantification and exploratory bulk RNA sequencing, performed at a single developmental time point using one pooled organoid RNA sample from each genotype, identify coordinated remodeling of neuronal and metabolic programs, along with junction-centered splicing dysregulation involving 6,310 differentially used junctions. Computational structural docking situates HNRNPH2 RNA recognition motifs (RRMs) 1-3 within a spliceosomal context and locates residue R114 near a predicted RNA-contact interface, indicating that the R114W substitution may alter RNA engagement. Integration of differential expression with event- and isoform-level analyses identifies regulatory hubs enriched for axon guidance and synaptic signaling pathways. Single-cell-reference-based deconvolution suggests modest compositional shifts that are unlikely to account for the extent of transcriptional and splicing alterations observed. Collectively, these findings implicate HNRNPH2-R114W in widespread RNA rewiring and define candidate isoform-level endpoints for mechanistic and therapeutic investigation in human cortical organoids. These molecular signatures open new avenues to examine how HNRNPH2-associated RNA dysregulation evolves across developmental time and recurs across independent biological contexts, providing a foundation for further mechanistic studies of this rare neurodevelopmental disorder.

  单细胞计算与 AI
• 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.
• KIF1A p.T258M Impairs Neural Progenitor Differentiation and Axonal Transport Through Dysregulated Wnt/β-Catenin–BDNF Signaling
  GSE348793Homo sapiens6 个样本2026-10-31

  Human neural stem cells were derived from KIF1A p.T258M-mutant induced pluripotent stem cells and CRISPR-Cas9-corrected isogenic control cells. RNA sequencing was performed to compare global gene expression profiles between KIF1A-mutant and control neural stem cells. Differentially expressed genes were identified and used for downstream GO and KEGG pathway enrichment analyses to explore molecular pathways associated with KIF1A mutation-induced neural developmental defects.
• 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.
• Single-cell regulatory genomics reveals coordinated myeloid and T-cell reprogramming in liver cirrhosis
  GSE348509Homo sapiens6 个样本2026-10-31

  We performed single-cell RNA sequencing (scRNA-seq) on liver tissues from 3 cirrhotic patients and 3 non-cirrhotic controls, analyzing 43,745 high-quality cells. We investigated cellular composition, SCENIC regulon activity, pseudotime trajectories, and CellChat communication. Cirrhosis was associated with Mono1 depletion, expansion of inflammatory macrophages and regulatory T cells, dysregulated YY1/ETV6 regulons in myeloid cells, altered EOMES/KLF6 programs in cytotoxic T cells, and increased EP300/SP3 in Tregs, along with fibrosis-biased ligand-receptor signaling. Note: Raw sequencing data are not available because the sequencing company routinely clears data after two years; only processed expression matrices are provided.

  单细胞
• 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.
• Transcriptomic profiling of human lymphocytes treated with 2'-deoxyinosine reveals immunomodulatory mechanisms relevant to multiple sclerosis
  GSE347378Homo sapiens9 个样本2026-10-31

  2'-Deoxyinosine (2'-DI) is an endogenous nucleoside formed by the deamination of deoxyadenosine by adenosine deaminase, and nucleoside metabolism pathways are involved in the initiation and progression of Multiple Sclerosis (MS). Our previous study indicated that 2'-DI treatment alleviates disease severity in an MS mouse model. To explore the potential preventive therapeutic mechanism of 2'-DI, we performed RNA sequencing on human lymphocytes isolated from MS patients. Cells were stimulated with OKT3 and treated with 0, 0.5, or 1 mM 2'-DI. Results showed that 2'-DI exposure induced dose-dependent transcriptomic changes. Differentially expressed genes were significantly enriched in immune-related pathways, including chemokine signaling pathway, cytokine-cytokine receptor interaction, and IL-17 signaling pathway, suggesting that 2'-DI may exert a protective effect in MS by finely regulating inflammatory immune responses.
• 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 [CC-Seq]
  GSE346184Saccharomyces cerevisiae114 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.
• 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.
• Gene transcription and chromatin packing domains form a self-organizing system [RIP-Seq]
  GSE345114Homo sapiens6 个样本2026-10-31

  The human genome organizes into several thousand chromatin packing domains that couple euchromatin and heterochromatin into unified nanoscale volumes. Prior work suggested these domains form by transcriptionally driven loops that guide packing domain assembly. Here, we study the process of transcriptionally driven domain formation and maintenance. By pairing auxin-inducible degron technology with nanoscopic imaging, transcriptomics, and Hi-C, we show that Pol-II regulates conformationally defined interphase chromatin packing domains. Pol-II facilitates nascent domain generation and maintains mature domain integrity through the process of generating transcriptional loops. Mechanistically, Pol-II maintains the packing of intronic and intergenic chromatin within domains by transcribing exons within gene bodies. Consequently, polymerase loss disrupts genome connectivity, in situ packing domains, and gene expression, genome-wide. Our findings suggest chromatin packing domains and RNA synthesis are tightly coupled to optimize transcriptional responses in human cells.
• Gene transcription and chromatin packing domains form a self-organizing system [EU-Seq]
  GSE345113Homo sapiens7 个样本2026-10-31

  The human genome organizes into several thousand chromatin packing domains that couple euchromatin and heterochromatin into unified nanoscale volumes. Prior work suggested these domains form by transcriptionally driven loops that guide packing domain assembly. Here, we study the process of transcriptionally driven domain formation and maintenance. By pairing auxin-inducible degron technology with nanoscopic imaging, transcriptomics, and Hi-C, we show that Pol-II regulates conformationally defined interphase chromatin packing domains. Pol-II facilitates nascent domain generation and maintains mature domain integrity through the process of generating transcriptional loops. Mechanistically, Pol-II maintains the packing of intronic and intergenic chromatin within domains by transcribing exons within gene bodies. Consequently, polymerase loss disrupts genome connectivity, in situ packing domains, and gene expression, genome-wide. Our findings suggest chromatin packing domains and RNA synthesis are tightly coupled to optimize transcriptional responses in human cells.
• Gene transcription and chromatin packing domains form a self-organizing system [CUT&Tag]
  GSE345111Homo sapiens1 个样本2026-10-31

  The human genome organizes into several thousand chromatin packing domains that couple euchromatin and heterochromatin into unified nanoscale volumes. Prior work suggested these domains form by transcriptionally driven loops that guide packing domain assembly. Here, we study the process of transcriptionally driven domain formation and maintenance. By pairing auxin-inducible degron technology with nanoscopic imaging, transcriptomics, and Hi-C, we show that Pol-II regulates conformationally defined interphase chromatin packing domains. Pol-II facilitates nascent domain generation and maintains mature domain integrity through the process of generating transcriptional loops. Mechanistically, Pol-II maintains the packing of intronic and intergenic chromatin within domains by transcribing exons within gene bodies. Consequently, polymerase loss disrupts genome connectivity, in situ packing domains, and gene expression, genome-wide. Our findings suggest chromatin packing domains and RNA synthesis are tightly coupled to optimize transcriptional responses in human cells.
• Id2 orchestrates IL-33-driven metabolic reprogramming in pathogenic Th2 cells (RNA-seq)
  GSE344612Mus musculus8 个样本2026-10-31

  The transcription factor Id2 licenses the transition of stem‑like Th2 cells to pathogenic ST2⁺ Tpath2 cells by orchestrating IL‑33‑ST2 signaling to drive glycolytic reprogramming. Id2 transcriptionally represses Pten by sequestering E proteins at its promoter, amplifying PI3K‑AKT signaling and glycolytic flux, which supports histone acetylation at Il1rl1 and Il5. Id2‑deficient Th2 cells fail to establish this epigenetic state; pyruvate supplementation rescues the defect. Pharmacological Id2 inhibition attenuates Tpath2 responses and airway inflammation in vivo, and cross‑species analysis confirms conserved PTEN dynamics in human asthma. Thus, the IL‑33–Id2–PI3K‑AKT axis represents a metabolic–epigenetic checkpoint and therapeutic target for allergic airway disease.
• Immune activation during broadly neutralizing antibody-mediated HIV suppression prior to post-intervention control
  GSE344609Homo sapiens52 个样本2026-10-31

  Broadly neutralizing antibodies (bNAbs) have been associated with enhancement of HIV-specific T or B cell responses and sustained partial control of HIV replication in some people with HIV (PWH). The mechanisms through which bNAbs may potentiate host immunity in this context are not known. We previously reported the outcomes of a clinical trial in which ten PWH on antiretroviral therapy (ART) received a combination of immunotherapies including two bNAbs administered immediately preceding an analytic treatment interruption (ATI). After bNAb levels waned, seven participants exhibited varying degrees of post-intervention control of HIV linked to a robust expansion of activated CD8+ T cells in response to rebounding virus. To investigate the role of the bNAbs in enhancing endogenous immune responses, we looked for evidence of HIV-specific or broader immune activation during the period after ART was paused and prior to rebound when bNAbs were controlling HIV replication. At a timepoint early post-ART interruption and at least one month before virus emerged in plasma, we detected an increase in levels of plasma inflammatory proteins as well as phenotypic and transcriptional activation of innate and adaptive immune cells. Compared to non-controllers, post-intervention controllers demonstrated unique transcriptional activation patterns as well as differential longitudinal plasma inflammatory protein trends. No enhancement of HIV-specific T cell or antibody responses was observed in this window. This study identifies activated cell types and inflammatory pathways that are recruited early during bNAb-mediated HIV suppression and that may play a role in potentiating long-lasting HIV immune control after bNAb therapy.
• 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.
• Local effect of Ixodes scapularia TNFBP gene silence on transcriptome of bitten skin of mouse
  GSE344220Mus musculus9 个样本2026-10-31

  To explore their potential role in tick-host interactions, RNA-seq was performed on the skin of mice bitten by TNFBP1 and TNFBP2 silenced ticks. The transcriptome was altered after feeding on gene silenced ticks compared with control ticks, and defined pathways including legionellosis, HIF-1TNF, IL-17 signaling pathway, phagosome were significantly enriched in the downregulated genes.
• PODXL regulates the neuronal entry of α-Synuclein aggregates
  GSE342465Homo sapiens6 个样本2026-10-31

  The spread of pathogenic α-synuclein assemblies between cells is thought to contribute to the progression of Parkinson’s disease, but the neuronal surface factors that control their uptake are still incompletely understood. To address this question, we established an arrayed CRISPR activation platform in human iPSC-derived cortical neurons and quantified the internalization of fluorescent α-synuclein preformed fibrils by high-throughput flow cytometry. Screening Parkinson’s disease genetics-prioritized surface proteins revealed podocalyxin-like protein 1 (PODXL) as a prominent negative regulator of fibril uptake.
• 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.
• Specification of bone marrow sinusoids requires TIE2-mediated positive feedback involving COUP-TFII and VEGFR3 [Nr2f2_ecko P5bm]
  GSE342123Mus musculus6 个样本2026-10-31

  The bone marrow (BM) vascular network drives bone development and supports hematopoiesis, yet the mechanisms governing its specialized sinusoidal architecture remain poorly characterized. Here, we show that the angiopoietin receptor TIE2 is highly expressed by BM sinusoidal endothelial cells (BM_SECs), and its endothelial deletion triggers sinusoidal capillarization, characterized by reduced vessel diameter and aberrant mural cell coverage. Mechanistically, TIE2 insufficiency drives a downregulation of VEGFR3 in BM_SECs, while leaving hepatic sinusoidal VEGFR3 unaffected. Notably, BM sinusoidal VEGFR3 downregulation occurred within 48 hours of induced endothelial Tek deletion. RNA-sequencing revealed that TIE2 insufficiency downregulated pathways related to sinusoidal development, alongside an aberrant upregulation of arterial and angiogenic genes. We validated this phenotype using inducible Tek deletion specifically within VEGFR3+ SECs, or in mutant mice with the insufficiency of TIE2 ligand ANGPT1. Furthermore, endothelial deletion of the transcription factor Nr2f2 (COUP-TFII) recapitulated these defects, yielding reductions in BM sinusoidal TIE2 and VEGFR3 expression. Finally, induced endothelial deletion of Flt4 produced a similar phenotype of defective BM sinusoidal formation. Together, our findings demonstrate that ANGPT1/TIE2 and COUP-TFII form a reciprocal regulatory loop essential for coordinating BM sinusoidal specification by sustaining VEGFR3 expression.
• Specification of bone marrow sinusoids requires TIE2-mediated positive feedback involving COUP-TFII and VEGFR3 [Tek_ecko P3bm]
  GSE342122Mus musculus8 个样本2026-10-31

  The bone marrow (BM) vascular network drives bone development and supports hematopoiesis, yet the mechanisms governing its specialized sinusoidal architecture remain poorly characterized. Here, we show that the angiopoietin receptor TIE2 is highly expressed by BM sinusoidal endothelial cells (BM_SECs), and its endothelial deletion triggers sinusoidal capillarization, characterized by reduced vessel diameter and aberrant mural cell coverage. Mechanistically, TIE2 insufficiency drives a downregulation of VEGFR3 in BM_SECs, while leaving hepatic sinusoidal VEGFR3 unaffected. Notably, BM sinusoidal VEGFR3 downregulation occurred within 48 hours of induced endothelial Tek deletion. RNA-sequencing revealed that TIE2 insufficiency downregulated pathways related to sinusoidal development, alongside an aberrant upregulation of arterial and angiogenic genes. We validated this phenotype using inducible Tek deletion specifically within VEGFR3+ SECs, or in mutant mice with the insufficiency of TIE2 ligand ANGPT1. Furthermore, endothelial deletion of the transcription factor Nr2f2 (COUP-TFII) recapitulated these defects, yielding reductions in BM sinusoidal TIE2 and VEGFR3 expression. Finally, induced endothelial deletion of Flt4 produced a similar phenotype of defective BM sinusoidal formation. Together, our findings demonstrate that ANGPT1/TIE2 and COUP-TFII form a reciprocal regulatory loop essential for coordinating BM sinusoidal specification by sustaining VEGFR3 expression.