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。

• Single-cell RNA sequencing of appendiceal adenocarcinoma reveals a low proportion of epithelial cells and a fibroblast enriched tumor microenvironment
  GSE352702Homo sapiens4 个样本2026-10-31

  Appendiceal adenocarcinoma (AA) is an understudied gastrointestinal malignancy. Treatment is guided by its proximal counterpart, colorectal cancer (CRC), despite recent studies demonstrating AA’s unique mutational landscape and poor response to CRC chemotherapy. As the first application of single-cell technology to AA these data provide insight into the intratumor heterogeneity of AA and highlight the important contribution of the tumor microenvironment in this orphan disease. These results also reinforce multiple observations that AA is a unique disease entity from CRC and targeting the tumor microenvironment should be considered as a therapeutic strategy.

  单细胞
• 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
• Local and circulating cytotoxic CD4 T cells are early markers of disease activity in pediatric Crohn’s disease
  GSE352630Homo sapiens8 个样本2026-10-31

  Inflammatory bowel disease (IBD) requires improved molecular and cellular stratification to guide therapy. In the PREDICT study, we profiled intestinal and blood T cells from treatment-naïve pediatric patients with IBD, disorders of gut–brain interaction controls, and healthy donors using single-cell RNA sequencing. Across 107 participants, we identify a population of clonally expanded cytotoxic CD4 T cells (CD4 CTL) enriched in the inflamed gut of patients with Crohn's disease (CD) and ulcerative colitis. Cell–cell interaction analyses and validation in a mouse model implicate IL-27 in CD4 CTL differentiation. Elevated CD4 CTL frequencies in gut and peripheral blood at diagnosis are associated with subsequent poor outcome of anti-TNF therapy in pediatric CD. Findings in our identification cohort are validated in an independent cohort and through reanalysis of published datasets. Blood CD4⁺CXCR6⁺CD27⁻ T cells displayed a CD4 CTL transcriptional phenotype, supporting CD4 CTLs as a candidate blood-accessible biomarker for treatment stratification.

  单细胞
• Transcriptomic profiling of Gem-miR-15a treatment in parental and drug resistant HCT116 colorectal cancer cells
  GSE352606Homo sapiens4 个样本2026-10-31

  Resistance to 5-fluorouracil (5-FU)-based chemotherapy is a major obstacle in colorectal cancer (CRC). Gem-miR-15a, a gemcitabine-modified tumor-suppressor microRNA-15a mimic, was developed to overcome chemoresistance by combining the tumor-suppressive activity of miR-15a with the cytotoxic activity of gemcitabine in a single, vehicle-free molecule. To investigate the transcriptomic basis of its activity and its ability to reverse resistance-associated gene expression, RNA-sequencing was performed on parental and 5-FU-resistant HCT116 CRC cells under untreated and Gem-miR-15a-treated conditions. Analysis of these profiles identified modulation of key oncogenic and stress-response pathways and reversal of resistance-associated expression patterns following Gem-miR-15a treatment.
• 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.
• Baseline immune transcriptional states predict future HIV-1 acquisition in individuals at risk of sexual infection
  GSE352331Homo sapiens104 个样本2026-10-31

  Natural resistance to HIV-1 acquisition in highly exposed seronegative (HESN) individuals suggests the existence of pre-existing host states associated with reduced susceptibility. However, the baseline molecular determinants of susceptibility remain poorly understood. We analyzed PBMC transcriptomes by RNA sequencing in 104 HIV-1-seronegative men who have sex with men (MSM) at high risk of sexual exposure, including 65 HESN and 39 who subsequently seroconverted. Differential expression, functional enrichment, and spatial genomic clustering analyses were integrated with Elastic Net regularized logistic regression. HESN individuals showed enrichment of sensory receptor (p.adj=2×10⁻¹⁶) and cell-adhesion pathways (p.adj=9×10⁻³), together with non-random genomic clustering (p.adj=1×10⁻⁴) of differentially expressed genes at immune-related loci, including TCR, IGH, KIR, and MHC/HLA regions. In contrast, future seroconverters exhibited increased mRNA metabolism (p.adj=1.5×10⁻¹⁴), immune activation (p.adj=0.01), and type I interferon signaling (p.adj=0.02). A 14-gene risk score showed an out-of-fold AUC of 0.888. Cross-cohort transportability was evaluated in an independent ectocervical RNA-seq dataset. Applied without refitting, the signature showed moderate discrimination between long-term HESN and HIV-negative women at high risk of acquisition (AUC=0.689). The out-of-fold molecular risk score was also associated with time to HIV-1 seroconversion in MSM (log-rank p=7.1×10⁻¹¹; score×time interaction p=0.0086). These findings identify distinct pre-infection transcriptional states associated with HIV-1 acquisition and support partially transportable transcriptional architecture across blood and genital mucosal compartments.

  空间转录组
• Longitudinal Gene Expression Profiling Reveals Molecular Evolution and Transcriptional Reprogramming During Multiple Myeloma Relapse
  GSE352244Homo sapiens105 个样本2026-10-31

  This study aims to characterize gene expression alterations associated with multiple myeloma (MM) relapse by performing longitudinal gene expression profiling (GEP) of CD138+ plasma cells isolated from bone marrow mononuclear cells collected from 35 patients at baseline, first relapse, and second relapse.
• 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.
• Overexpression of IL-1Ra in MSCs Ameliorates Hepatic Injury via GGT5 and Improves Survival of aGVHD Mice
  GSE351748Homo sapiens6 个样本2026-10-31

  In conclusion, oeIL_x001E_1Ra_x001E_MSCs alleviate aGVHD_x001E_related hepatic lesions through anti_x001E_inflammatory effects and GGT5_x001E_dependent maintenance of redox and mitochondrial homeostasis, offering a promising cell_x001E_therapy strategy and theoretical foundation for targeted treatment of hepatic aGVHD.
• Spatial transcriptomic analysis of fibroblast therapy with collagen/PMMA in human skin [Xenium]
  GSE350895Homo sapiens3 个样本2026-10-31

  Xenium spatial transcriptomic analysis was performed to investigate cellular responses and tissue remodeling following fibroblast therapy with or without collagen/PMMA in human skin.

  空间转录组
• Collagen-PMMA scaffolds induce dermal remodeling and immune recruitment distinct from simple volar fibroblast therapy in human skin [scRNAseq]
  GSE350894Homo sapiens3 个样本2026-10-31

  Cellular therapy is promising but requires optimization in human subjects. Volar skin of the palms and soles is adapted to mechanical stress through a thick epidermis and dense extracellular matrix, whereas non-volar skin is vulnerable at high-pressure sites such as prosthetic limb interfaces. Because volar fibroblasts can partially reprogram non-volar skin, we tested whether collagen/polymethyl methacrylate (PMMA) could enhance volar fibroblast therapy. Healthy volunteers received vehicle, scalp fibroblast, or volar fibroblast injections, with or without collagen/PMMA, into non-volar skin. Durometer, optical coherence tomography, histology, and transcriptomic analyses showed volar-like structural changes and activation of skin-development, keratinocyte-differentiation, extracellular-matrix, and morphogenesis pathways. Collagen/PMMA promoted fibroblast, immune, and endothelial cell accumulation, consistent with a scaffold-associated tissue response. These findings distinguish volar fibroblast–associated skin identity changes from collagen/PMMA-induced stromal remodeling with foreign body, inflammatory, and fibrotic/myofibroblast-associated features.

  单细胞
• 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.
• 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.
• 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
• 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.
• 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.
• 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.
• 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.
• 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.
• A Viral Replication Level-Dependent Continuum of Transcriptional and MicroRNA Reprogramming in HIV-1-Infected Microglia Links Productive Infection to Neurocognitive-Associated Gene Networks [RNA-seq]
  GSE341759Homo sapiens8 个样本2026-10-31

  Microglia are major targets of HIV-1 in the brain. Despite the effectiveness of antiviral therapy, infected microglia, including those containing a replication-defective provirus, can express viral RNA and proteins that contribute to neuroinflammation. However, the degree to which productive infection shapes the host response in microglia remains poorly defined. Using single cell RNA-seq of HIV-1-infected C20 microglia, we stratified cells by counts of HIV-1 reads with splice junctions into low- and high-infection groups, enabling us to resolve a graded rather than binary host transcriptional response. A core set of immune and cell-cycle pathways was induced regardless of infection level, but several programs reversed direction with increasing viral burden: interferon-α/γ and EMT/hypoxia signatures peaked at low infection, while high infection was marked by suppression of these signatures alongside induction of mTORC1/MYC signaling, ribosome biogenesis, RNA processing, and mitotic activity, accompanied by progressive loss of cytoskeletal, motility, and developmental gene programs. This pattern was reproduced in iPSC-derived microglia, supporting its generalizability beyond an immortalized line. Integration of differentially expressed miRNAs with differentially expressed genes from the low- and high-infection groups showing the canonical inverse miRNA-target relationship revealed miRNA/mRNA networks with strong representation of miRNAs previously implicated in HIV-1 replication (e.g., miR-33a-5p, miR-3065-3p) and in neurodegenerative and psychiatric disease (e.g., miR-107, let-7c-5p). These findings define a productive-infection-level continuum in microglial transcription, miRNA reprogramming, and identify candidate miRNA-mediated mechanisms, independent of the canonical Env/Nef/Tat pathway, by which HIV-1-infected microglia may contribute to neuroinflammation and neurocognitive impairment in people with HIV-1.

  单细胞
• A Viral Replication Level-Dependent Continuum of Transcriptional and MicroRNA Reprogramming in HIV-1-Infected Microglia Links Productive Infection to Neurocognitive-Associated Gene Networks [scRNA-seq]
  GSE341758Homo sapiens6 个样本2026-10-31

  Microglia are major targets of HIV-1 in the brain. Despite the effectiveness of antiviral therapy, infected microglia, including those containing a replication-defective provirus, can express viral RNA and proteins that contribute to neuroinflammation. However, the degree to which productive infection shapes the host response in microglia remains poorly defined. Using single cell RNA-seq of HIV-1-infected C20 microglia, we stratified cells by counts of HIV-1 reads with splice junctions into low- and high-infection groups, enabling us to resolve a graded rather than binary host transcriptional response. A core set of immune and cell-cycle pathways was induced regardless of infection level, but several programs reversed direction with increasing viral burden: interferon-α/γ and EMT/hypoxia signatures peaked at low infection, while high infection was marked by suppression of these signatures alongside induction of mTORC1/MYC signaling, ribosome biogenesis, RNA processing, and mitotic activity, accompanied by progressive loss of cytoskeletal, motility, and developmental gene programs. This pattern was reproduced in iPSC-derived microglia, supporting its generalizability beyond an immortalized line. Integration of differentially expressed miRNAs with differentially expressed genes from the low- and high-infection groups showing the canonical inverse miRNA-target relationship revealed miRNA/mRNA networks with strong representation of miRNAs previously implicated in HIV-1 replication (e.g., miR-33a-5p, miR-3065-3p) and in neurodegenerative and psychiatric disease (e.g., miR-107, let-7c-5p). These findings define a productive-infection-level continuum in microglial transcription, miRNA reprogramming, and identify candidate miRNA-mediated mechanisms, independent of the canonical Env/Nef/Tat pathway, by which HIV-1-infected microglia may contribute to neuroinflammation and neurocognitive impairment in people with HIV-1.

  单细胞
• A Viral Replication Level-Dependent Continuum of Transcriptional and MicroRNA Reprogramming in HIV-1-Infected Microglia Links Productive Infection to Neurocognitive-Associated Gene Networks [miRNA-seq]
  GSE341757Homo sapiens4 个样本2026-10-31

  Microglia are major targets of HIV-1 in the brain. Despite the effectiveness of antiviral therapy, infected microglia, including those containing a replication-defective provirus, can express viral RNA and proteins that contribute to neuroinflammation. However, the degree to which productive infection shapes the host response in microglia remains poorly defined. Using single cell RNA-seq of HIV-1-infected C20 microglia, we stratified cells by counts of HIV-1 reads with splice junctions into low- and high-infection groups, enabling us to resolve a graded rather than binary host transcriptional response. A core set of immune and cell-cycle pathways was induced regardless of infection level, but several programs reversed direction with increasing viral burden: interferon-α/γ and EMT/hypoxia signatures peaked at low infection, while high infection was marked by suppression of these signatures alongside induction of mTORC1/MYC signaling, ribosome biogenesis, RNA processing, and mitotic activity, accompanied by progressive loss of cytoskeletal, motility, and developmental gene programs. This pattern was reproduced in iPSC-derived microglia, supporting its generalizability beyond an immortalized line. Integration of differentially expressed miRNAs with differentially expressed genes from the low- and high-infection groups showing the canonical inverse miRNA-target relationship revealed miRNA/mRNA networks with strong representation of miRNAs previously implicated in HIV-1 replication (e.g., miR-33a-5p, miR-3065-3p) and in neurodegenerative and psychiatric disease (e.g., miR-107, let-7c-5p). These findings define a productive-infection-level continuum in microglial transcription, miRNA reprogramming, and identify candidate miRNA-mediated mechanisms, independent of the canonical Env/Nef/Tat pathway, by which HIV-1-infected microglia may contribute to neuroinflammation and neurocognitive impairment in people with HIV-1.

  单细胞