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。

• Transcriptomic Insights into Cleidocranial Dysplasia Pathogenesis in Alveolar Bone Mesenchymal Stem Cells
  GSE297061Homo sapiens16 个样本2026-10-28

  Cleidocranial dysplasia (CCD) is a genetic disorder that primarily impacts skeletal and dental development, often leading to unerupted teeth due to impaired alveolar bone remodeling. This study investigates the transcriptomic profiles of alveolar bone-derived mesenchymal stem cells (aBMSCs) from CCD patients and unaffected controls to elucidate the molecular mechanisms underlying these dental defects. aBMSCs were isolated from two unrelated CCD patients with confirmed RUNX2 variants (c.673C>T, p.(Arg225Trp) and c.739delA, p.(Ser247Valfs*3)) and from 10 controls. Cells were cultured under general and osteogenic conditions. RNA sequencing, qRT-PCR, and bioinformatic analyses were used to assess gene expression profiles and validate key findings.CCDs exhibited significant dysregulation of ECM genes, including downregulation of COL1A1, COL3A1, and COL5A1 during osteogenic differentiation, indicating impaired bone formation. Disruptions in key signaling pathways, such as G protein-coupled receptor and prostaglandin signaling, highlighted broader osteogenic regulatory perturbations. CCDs displayed distinct transcriptional responses to osteogenic induction, with numerous DEGs, but no single gene was consistently dysregulated across all CCD-control comparisons, reflecting inter-individual heterogeneity. Notably, LGR4, PPP1R12B, PTGER2, and PTGS1 were consistently dysregulated in CCD under both basal and osteogenic conditions, with inverse expression relative to controls. These genes may represent key molecular signatures of CCD and contribute to its phenotypic variability. These findings highlight disrupted ECM formation and transcriptional heterogeneity in CCD, reflecting the complex effects of distinct RUNX2 variants. Consistently dysregulated genes, including LGR4, PPP1R12B, PTGER2, and PTGS1, may serve as key markers of impaired osteogenesis and potential therapeutic targets.

  扰动筛选
• Transcriptomic Profiling of Primary Tumor, Brain Metastasis, and Normal Brain Tissues of Lung Adenocarcinoma (LUAD)
  GSE293159Homo sapiens12 个样本2026-10-28

  The objective of this sequencing was to investigate the differential molecular characteristics among primary LUAD, brain metastases (BrM), and normal brains. We aim to identify unique signatures and pathways involved in the metastatic progression of LUAD to the brain, potentially uncovering novel targets for therapeutic intervention.
• RNA-seq analysis after venetoclax and azacitidine treatment in AML cells
  GSE284469Homo sapiens18 个样本2026-10-28

  RNA-seq analysis was performed in three isogenic MOLM-13 acute myeloid leukemia (AML) cell lines (p53 WT/p53 R248Q/p53 KO) to analyze gene expression changes after treatment with venetoclax and azacitidine.
• Unveiling the role of UPF1-mediated mRNA decay in melanoma tumorigenesis by modulating the miR-101-3p/NANOS1 axis
  GSE267965Homo sapiens20 个样本2026-10-28

  Numerous studies have reported that Up-frameshift protein 1 (UPF1) as a crucial posttranscriptional regulator in nonsense-mediated mRNA decay (NMD), attributing its role to tumorigenesis across various cancers. However, its recently unveiled function in UPF1-mediated mRNA decay (UMD), intricately coordinated with miRNA, remains unexplored in the context of tumorigenesis. Herein, we elucidate the pivotal role of UPF1 in governing melanoma tumorigenesis by modulation of NANOS1 expression via miR-101-3p. Depletion of UPF1 across three melanoma cell lines significantly impaired cell growth, migration, and invasion by cell cycle arrest and disrupted tumor formation in vivo. Through comprehensive RNA-seq and biochemical analyses, we elucidate that attenuation of UPF1 leads to an increase in NANOS1 expression, consequently suppressing melanoma tumorigenesis. Mechanistically, UPF1 orchestrates the destabilization of NANOS1 via UPF1-mediated mRNA decay (UMD) facilitated by miR-101-3p. Intriguingly, our findings highlight a novel protein modification event involving the phosphorylation of ELK1 by the UPF1/miR-101-3p/NANOS1 pathway, as revealed by antibody microarray analysis. Importantly, our study underscores the significance of UPF1 and NANOS1 in regulating melanoma tumorigenesis, even in drug-resistant cell lines and in vivo models including syngeneic and xenograft mouse models. Collectively, these insights shed light on the role of UMD in melanoma tumorigenesis through the UPF1/NANOS1/miR-101-3p axis and unveil potential therapeutic strategies for both primary and drug-resistant melanoma treatment.
• Detailed characterization of the immune response to Epstein-Barr virus in multiple sclerosis and following B cell depleting treatment
  GSE352228Homo sapiens24 个样本2026-10-27

  B-cell-depleting therapies are increasingly used for the treatment of multiple sclerosis (MS). Here, we characterize the impact of BCDT on humoral and cellular immune response to Epstein-Barr virus (EBV) in persons with MS (pwMS). We find that EBV viral load does not differ between pwMS and HC. By contrast, distinct differences are found in both humoral and cellular EBV-specific immunity in MS. EBV-specific antibody titres are increased in pwMS, whereas cellular immunity diverges toward lower CD8+ T cell reactivity against lytic antigens, including BZLF1. Notably, during periods of disease activity, both CD4+ and CD8+ T cell responses to lytic antigens tend to be higher. In addition, BZLF1-specific T cell clones recognizing the peptide RAKFKQLL were the most clonally expanded population in the intrathecal compartment of a pwMS with high CSF T cell counts. BCDT reduces EBV viral load and is associated with pronounced reduction in CD8+ T cell responses to all lytic EBV antigens. These findings delineate distinct alterations in EBV-specific immunity in MS and demonstrate that BCDT modulates both viral load and T cell responses. The data support a potential role for CD8+ T cell clones targeting lytic EBV proteins in MS pathogenesis.
• Transcriptome-wide mapping reveals an RNA-dependent mechanism of platinum cancer drugs. [ptRNAseq_A2780_Fractionation]
  GSE352212Homo sapiens24 个样本2026-10-27

  Clinically used small molecules have been predicted to off-target to RNAs. However, the extent of this interaction is small molecule cancer therapeutics have not been characterized. Here, we screened for anticancer small molecules for their RNA interactions and uncovered widespread RNA off-targeting. Cisplatin was found to be one among the RNA binders. We used it as a model agent to identify the specific transcripts it interacts with. To accomplish this, we developed Plat-RNAseq, a click-chemistry-mediated transcriptome-wide assay. Our results revealed that cisplatin binding was enriched at guanine-rich regions capable of forming RNA G-quadruplexes (rG4s). We found that the recruitment of cisplatin to rG4s partially contributed to its cytotoxicity, revealing a noncanonical mechanism of action for this widely used chemotherapeutic agent. This experiment applied PlatRNA-seq to chromatin-associated, nuclear and cytoplasmic RNA fractions to assess whether platinum binding occurs co-transcriptionally or on mature RNA.
• Transcriptomics of human fetal microglia infected with HIV-1
  GSE351613Homo sapiens36 个样本2026-10-27

  This SuperSeries is composed of the SubSeries listed below.

  SuperSeries
• Transcriptomics of human fetal microglia infected with HIV-1 [V8 RNA-Seq]
  GSE351612Homo sapiens12 个样本2026-10-27

  Microglia act as HIV reservoirs in the brain and contribute to the development of HIV-associated neurocognitive disorders. Understanding the pathobiology of HIV-infected microglia is therefore essential. Here, we examined the transcriptome of primary microglia infected ex vivo with HIV-1. Analyses reveal a significant expression modulation of DNA/cell cycle, cellular stress-related, as well as non-membrane bounded organelle assembly-related genes, and a broad effect on microRNA expression. MicroRNA-23b is identified among upregulated microRNAs in HIV-1-infected microglia, and the downregulated g3bp2 mRNA validated as its target. G3BP2 is a component of stress granules (SGs), which serve as antiviral and proinflammatory platforms. MicroRNA-23b mimics reduce both SG assembly and G3BP2 expression in arsenite (As)-treated monocyte-derived microglial cells (MDMi), and few SGs aggregate in infected MDMi in response to As-mediated stress. MicroRNA-23b inhibitors partially re-establish SG formation and reduce HIV-1 replication and spread. Thus, microRNA-23b induction enables HIV-1 to counter SG assembly in infected microglia, a host response that restricts HIV-1 replication and ensuing neuropathogenesis
• Transcriptomics of human fetal microglia infected with HIV-1 [V6 miRNA-Seq]
  GSE351611Homo sapiens24 个样本2026-10-27

  Microglia act as HIV reservoirs in the brain and contribute to the development of HIV-associated neurocognitive disorders. Understanding the pathobiology of HIV-infected microglia is therefore essential. Here, we examined the transcriptome of primary microglia infected ex vivo with HIV-1. Analyses reveal a significant expression modulation of DNA/cell cycle, cellular stress-related, as well as non-membrane bounded organelle assembly-related genes, and a broad effect on microRNA expression. MicroRNA-23b is identified among upregulated microRNAs in HIV-1-infected microglia, and the downregulated g3bp2 mRNA validated as its target. G3BP2 is a component of stress granules (SGs), which serve as antiviral and proinflammatory platforms. MicroRNA-23b mimics reduce both SG assembly and G3BP2 expression in arsenite (As)-treated monocyte-derived microglial cells (MDMi), and few SGs aggregate in infected MDMi in response to As-mediated stress. MicroRNA-23b inhibitors partially re-establish SG formation and reduce HIV-1 replication and spread. Thus, microRNA-23b induction enables HIV-1 to counter SG assembly in infected microglia, a host response that restricts HIV-1 replication and ensuing neuropathogenesis
• Synapse-seq reveals cytotoxic CD4+ T cell suppression of human antibody responses
  GSE351507Homo sapiens22 个样本2026-10-27

  Deciphering the molecular dialogue between cells is central to understanding how immune responses are orchestrated. Here we applied Synapse‐seq, a new image‐enabled cell interaction sorting and transcriptomic profiling approach, to characterize CD4+ T-B cell synaptic interactions in human spleen organoids. We identified B cells synapsing with FOXP3+ regulatory T cells (Tregs) expressing high levels of perforin and granzymes A and B, indicating that cytotoxicity is a major mechanism of CD4+ Treg suppression of specific B cells. Antigen-specific Synapse-seq revealed opposing phenotypes of viral and autoreactive T-B interactions and identified a hemagglutinin-specific TCR-BCR pair in a human immune system. Both CD3+ and CD4+ T cell-specific knockouts of cytotoxic genes robustly increased antibody responses against both nuclear autoantigens and viral antigens. Consistent with these findings, patients with systemic lupus erythematosus (SLE) exhibited a significant enrichment of cytotoxic CD4+ Tregs. Our findings support cytotoxicity as a dominant way CD4+ T cells regulate B cells and antibody responses. More broadly, we suggest Synapse-seq as a generalizable method to characterize cell interactions without requiring cell engineering.
• Regulatory T Cell Instability Facilitates Blood-Brain Barrier Disruption via the β-catenin-Tight Junctions Axis, Leading to Perioperative Neurocognitive Disorders
  GSE337348Homo sapiens12 个样本2026-10-27

  Perioperative neurocognitive disorders (PND) are significant neurological complications in elderly surgical patients, yet the underlying immune-mediated mechanisms remain elusive. Blood-brain barrier (BBB) disruption is increasingly recognized as a critical neurovascular event in PND and may result from perioperative immune dysregulation. Regulatory T cells (Tregs) are key mediators of neurovascular homeostasis and BBB integrity. We therefore investigated whether perioperative Treg instability contributed to BBB disruption and PND. Single-cell transcriptomic profiling of perioperative PBMCs from elderly surgical patients revealed marked remodeling of the CD4+ T cell compartment, characterized by disproportionate Treg loss and functional destabilization. Tregs shifted from resting and immunosuppressive states toward an inflammatory phenotype, accompanied by reduced expression of regulatory and tissue-reparative genes, including FOXP3, CTLA4, PDCD1, and AREG. Comparative transcriptomic analysis of Tregs identified 34 dexmedetomidine-corrected genes, with CTNNB1, encoding β-catenin, emerging as the dominant hub within the protein-protein interaction network. These findings implicated impaired β-catenin signaling as a central driver of perioperative Treg destabilization. Mouse hippocampal scRNA-seq revealed postoperative endothelial remodeling characterized by reduced S1pr1 and Cldn5 and increased Icam1 expression. In a murine PND model, β-catenin activation restored postoperative Treg abundance and regulatory gene expression while preserving hippocampal endothelial barrier programs, as evidenced by increased S1PR1 and Claudin-5 and reduced ICAM1 expression. These protective effects were abolished by PC61-mediated Treg depletion, indicating a Treg-dependent mechanism. Furthermore, restoration of Treg homeostasis with recombinant PD-L1 preserved ultrastructural BBB integrity, reduced Evans blue-defined BBB leakage, attenuated hippocampal neuroinflammation, and improved cognitive function. These findings identify perioperative Treg instability as a key immune driver of BBB disruption and cognitive dysfunction in PND, and establish Treg β-catenin signaling as a potential therapeutic target for preserving neurovascular integrity.

  单细胞
• Bulk RNA-seq of monocytes from systemic lupus erythematosus samples
  GSE326771Homo sapiens10 个样本2026-10-27

  This study profiled bulk RNA-seq from human monocyte samples derived from individuals with systemic lupus erythematosus. Total RNA was extracted and sequenced to characterize transcriptomic features in SLE monocytes. Raw gene-level count matrices, gene annotation, and sample-level metadata are provided.
• Bulk RNA-seq of IFN-treated and untreated healthy control neutrophils
  GSE326770Homo sapiens12 个样本2026-10-27

  This study profiled bulk RNA-seq from human neutrophils derived from healthy control donors under untreated and IFN-treated conditions. Total RNA was extracted and sequenced to characterize transcriptional responses associated with IFN exposure. Raw and normalized gene-level count matrices, along with sample-level metadata and gene annotation files, are provided.
• 3D genome remodeling directs in vitro human hematopoietic development and predicts disease trait genetics
  GSE311714Homo sapiens14 个样本2026-10-27

  The 3D genomic architecture provides a regulatory scaffold for cell fate transitions, yet how chromatin architecture directs human hematopoietic development remains poorly understood. The endothelial-to-hematopoietic transition (EHT) is the developmental gateway by which specialized hemogenic endothelial cells generate definitive hematopoietic stem and progenitor cells (HSPCs), which go on to support blood cell production throughout mammalian life. Understanding mechanisms that regulate EHT is critical for blood disease modeling and regenerative medicine applications. Using a human induced pluripotent stem-cell (iPSC) hematopoiesis model, we combined single-nucleus RNA-seq, ATAC-seq, and Hi-C to chart chromatin reorganization during hemogenic specification and EHT. Hierarchical reorganization of topologically associating domains (TADs) and sub-TAD structures accompany the morphological conversion of endothelial sheets into HSPCs. Dynamic TAD and sub-TAD reorganization precedes transcriptional activation of key hematopoietic regulators (e.g., RUNX1, CEBPA), revealing a structural logic by which genome topology anticipates formation of cis-regulatory elements and transcription factor programs that control hematopoietic development. For example, we identify modulation of dynein and kinesin molecular motor genes during EHT. Functional dynein inhibition promotes EHT, likely through unopposed activities of kinesin motors. Integration of single cell data with Hi-C and genome-wide association study (GWAS) loci reveals enrichment for blood and immune trait variants, connecting 3D genome remodeling during in vitro hematopoiesis to in vivo human disease genetics. Together, these findings define the regulatory architecture of blood cell emergence and establish iPSC differentiation as a tractable platform for interrogating 3D genome principles in human development and disease. More broadly, our integrated data across rare developmental cell types helps define 3D chromatin regulatory architecture that underlies human GWAS variation.

  单细胞
• p53 preserves chromosome stability in dividing cells under hypo-osmotic stress
  GSE311220Homo sapiens30 个样本2026-10-27

  Cells respond to frequent osmotic stress to maintain structural integrity and function. Whereas acute volume regulation is well-known, the cellular response to prolonged osmotic stress and its long-term consequences remain poorly understood. In this study, we investigate how lasting hypo-osmotic stress influences cell proliferation and the associated cellular response. We observe that cells undergoing their first division under hypo-osmotic stress experience delayed mitotic entry, lengthened mitotic duration, elevated mitotic errors and aneuploidy formation. However, continued cell division is halted through a p53/p21-dependent G1 arrest. p53 activation occurs post-mitotically and is associated with loss of perichromosomal layer (PCL), defective chromosome decondensation and impaired nuclear expansion in daughter cells after mitotic exit. We show that the altered nuclear size dynamics lead to nuclear accumulation of p53 and activation of downstream gene expression. These findings uncover a mechanosensitive, p53-mediated mechanism that safeguards chromosome integrity by suppressing erroneous mitosis under hypo-osmotic stress.
• Chemically Defined Differentiation of Human PSCs to Definitive Hematopoietic Progenitors
  GSE304432Homo sapiens21 个样本2026-10-27

  This study investigates hematopoietic differentiation of human pluripotent stem cells (hPSCs) using a chemically defined differentiation system. RNA-seq was used to characterize cell populations generated during differentiation, including adherent supportive cells and suspension hematopoietic populations. The newly submitted samples provide additional transcriptomic profiling of FACS-sorted CD34+CD38-CD45RA-CD90+CD49f+ cells isolated from the suspension hematopoietic population and complement the other samples .
• SAA-expressing hepatocytes as a key liver cell population in Alcohol associated Hepatitis
  GSE304325Homo sapiens13 个样本2026-10-27

  This study describes the dynamics of cellular heterogeneity during the progression of ALD to AH at a single cell level. Moreover, we have identified the specific subpopulations enriched in AH. This condition is characterized by an expansion of proinflammatory SAA+ hepatocytes, which strongly interact with hyperactivated neutrophils, suggesting a potential mechanism that could contribute to the exacerbated inflammation that characterizes this disease.

  单细胞
• Effect of senescent cells on macrophage polarisation
  GSE296922Homo sapiens10 个样本2026-10-27

  Senescent cells (SCs) accumulate with age and injury and express a pro-inflammatory/pro-fibrotic secretome, termed the senescence-associated secretory phenotype (SASP). Hence, accumulation of senscent cells can lead to inflammation and organ fibrosis. To investigate effects of SASP factors on macrophage polarisation macrophages matured from healthy donor blood monocytes were exposed to control or senescent cell conditioning media for 24 hours. Senescent cell media was derived from human proximal tubular epithelial cells (PTECs) exposed to 10 Gy of ionising radiation to induce senescence in vitro.
• sn-multiome of psoriasis skin
  GSE294957Homo sapiens18 个样本2026-10-27

  We simultaneously profile the gene expression and chromatin accessibility of lesional skin of psoriasis to understand the epigenetic landscape that regulates gene expression in the psoriatic skin

  多组学
• Single Cell multi-omics identifies VEGFA-mediated angiogenesis results in relapse in Sonic Hedgehog Medulloblastoma [snRNA-seq]
  GSE287109Homo sapiens12 个样本2026-10-27

  Relapse in Sonic Hegdehog Medulloblastoma (SHH-MB) a common pediatric brain tumor, remain a significant clinical challenge due to its poor prognosis and limited therapeutic intervention. Understanding the underlying molecular mechanisms driving relapse is critical for developing targeted interventions. Here, we utilize single-cell multi-omics, combining single-nucleus RNA sequencing (snRNA-seq), single-nucleus ATAC sequencing (snATAC-seq), and spatial omics to comprehensively characterize the cellular landscape and regulatory networks associated with SHH medulloblastoma relapse. Our integrative analysis identifies distinct GCP population enriched with angiogenic activity characterized high expression of Vascular Endothelial Growth Factor A (VEGFA) regulated by the transcription factor HIF1A. Notably, we find that VEGFA-mediated angiogenesis is a critical driver of tumor recurrence, promoting a microenvironment that supports tumor revascularization and growth in the endothelial cells. Furthermore, we uncover potential therapeutic targets within the VEGFA signaling axis that could disrupt angiogenesis and reduce relapse rates. Our findings provide new insights into the molecular and cellular dynamics of SHH medulloblastoma relapse and highlight VEGFA as a key mediator of angiogenesis-driven recurrence, offering a promising avenue for therapeutic intervention.

  单细胞空间转录组多组学
• Single Cell multi-omics identifies VEGFA-mediated angiogenesis results in relapse in Sonic Hedgehog Medulloblastoma
  GSE287108Homo sapiens13 个样本2026-10-27

  Relapse in Sonic Hegdehog Medulloblastoma (SHH-MB) a common pediatric brain tumor, remain a significant clinical challenge due to its poor prognosis and limited therapeutic intervention. Understanding the underlying molecular mechanisms driving relapse is critical for developing targeted interventions. Here, we utilize single-cell multi-omics, combining single-nucleus RNA sequencing (snRNA-seq), single-nucleus ATAC sequencing (snATAC-seq), and spatial omics to comprehensively characterize the cellular landscape and regulatory networks associated with SHH medulloblastoma relapse. Our integrative analysis identifies distinct GCP population enriched with angiogenic activity characterized high expression of Vascular Endothelial Growth Factor A (VEGFA) regulated by the transcription factor HIF1A. Notably, we find that VEGFA-mediated angiogenesis is a critical driver of tumor recurrence, promoting a microenvironment that supports tumor revascularization and growth in the endothelial cells. Furthermore, we uncover potential therapeutic targets within the VEGFA signaling axis that could disrupt angiogenesis and reduce relapse rates. Our findings provide new insights into the molecular and cellular dynamics of SHH medulloblastoma relapse and highlight VEGFA as a key mediator of angiogenesis-driven recurrence, offering a promising avenue for therapeutic intervention.

  单细胞空间转录组多组学
• Expression profile of tumor suppressive miR-34a- and DNA demethylase TET1-overexpressing MDA-MB-231 metastatic breast cancer cell lines in response to MCTS1 enrichment
  GSE247305Homo sapiens12 个样本2026-10-27

  Small, single-stranded, non-coding microRNA-34a (miR-34a) has been reported to inhibit tumorigenesis in many types of cancers. We previously reported that miR-34a is one of the most upregulated miRNAs upon the depletion of Malignant T-cell amplified sequence (MCT-1 or MCTS1), a proto-oncoprotein containing RNA-binding domain PUA. We hypothesized that MCTS1 inhibits miR-34a expression by downregulating DNA demethylation machinery, ten eleven translocation 1 (TET1). By using RNA-seq, we aimed to dissect differential downstream targets implicated by abberant MCTS1 in breast cancer cells with enrichment of tumor suppressors miR-34a and TET1.
• Cytoprotective Effects of Quercetin on Antibiotics- and Antimycotics-Induced Toxicity in Human Corneal Epithelial Cells: Cellular Responses and Transcriptomic Mechanisms
  GSE351741Homo sapiens12 个样本2026-10-26

  Quercetin, a plant-derived dietary flavonoid with well-studied antioxidant properties, was shown to have cytoprotective effects against several cytotoxic drugs, yet its potential for antimicrobial-induced cytotoxicity on corneal epithelium remains unexplored. The corneal epithelium, in synergy with the secretions of lacrimal and meibomian glands, maintains the ocular surface homeostasis and integrity. Constant environmental exposure predisposes the ocular surface to microbial keratitis, which is routinely treated with antibiotics and antimycotics. Prolonged use of antimicrobials induces epithelial cell death and chronic conditions such as dry eye disease. In this study, human corneal epithelial (HCE) cells were treated with the antibiotics ciprofloxacin (CIP) and moxifloxacin (MXF) and the antimycotics fluconazole (FLU) and natamycin (NAT), alone and in combination with quercetin, and cytotoxicity, apoptotic markers, and whole-transcriptome changes were assessed. All four antimicrobials induced significant, concentration-dependent cytotoxicity at therapeutic doses, evidenced by apoptotic morphology, elevated BAX/Bcl-2 ratio, and increased sub-G0/G1 and Annexin V-positive populations. Quercetin co-treatment markedly attenuated cell death by reversing apoptotic signatures and transcriptomic reversal of multiple antimicrobial-induced signaling pathways. These findings demonstrate the cytoprotective capacity of the natural antioxidant quercetin against antibiotic- and antimycotic-induced cytotoxicity in HCE cells, supporting its translational potential as a natural antioxidant adjuvant in antimicrobial ophthalmic formulations.
• Transcriptomic profiling of Niemann-Pick disease type C (NPC1-mutant) patient fibroblasts and healthy control fibroblasts with and without Fingolimod treatment
  GSE351603Homo sapiens12 个样本2026-10-26

  Niemann-Pick disease type C (NPC) is a rare lysosomal storage disorder caused by mutations in NPC1, which impair cholesterol export from late endosomes/lysosomes and lead to progressive neurodegeneration. How lysosomal cholesterol trafficking failure translates into broader cellular dysfunction, and whether it can be pharmacologically reversed, remains poorly understood. Fingolimod (FTY720), an FDA-approved sphingosine-1-phosphate receptor modulator, has been reported to improve lipid trafficking in NPC1-deficient cells. To define the transcriptional consequences of NPC1 deficiency and the response to Fingolimod, we performed bulk RNA-seq on primary skin fibroblasts from an NPC patient and a healthy control, each untreated or treated with Fingolimod. NPC fibroblasts showed widespread transcriptional reprogramming compared with healthy control fibroblasts, including dysregulation of lysosomal, autophagy and cholesterol homeostasis genes, activation of innate immune and interferon-stimulated genes, altered DNA repair gene expression, loss of fibroblast identity programs, and induction of a transcriptomic aging signature. Fingolimod treatment partially reversed many of these disease-associated changes in NPC fibroblasts, shifting the transcriptome toward that of healthy controls and reducing the transcriptomic aging score, and also lowered the aging score in healthy control fibroblasts. These data support a link between lysosomal cholesterol trafficking failure, innate immune activation and cellular aging signatures, and identify Fingolimod as a modulator of these programs.
• TGF-β inhibition ameliorates reactive ALS astrocyte sub-states at single-cell resolution
  GSE351508Homo sapiens16 个样本2026-10-26

  In amyotrophic lateral sclerosis (ALS), astrocytes become reactive, ultimately contributing to neuron death. Upregulation of TGF-β signalling has been implicated in astrocyte-mediated neurodegeneration in ALS. However, whether TGF-β drives cell-autonomous astrocyte reactive transformation, potentially by altering astrocyte reactive substates, remains unknown. To address this, we inhibited TGF-β in hiPSC derived ALS astrocytes carrying VCP mutations, known to cause familial ALS, and performed single-cell RNA sequencing, single-cell proteomics and functional studies informed by our analysis. We identified changes in the proportion of transcriptomic reactive substates characterised by mitochondrial dysfunction and markers of reactive transformation. Importantly these substates selectively upregulated an isoform-restricted TGF-β2–betaglycan axis and were ameliorated following TGF-β inhibition. Single-cell mass spectrometry-based proteomics validated these findings, revealing a VCP mutant subpopulation featuring increased translation and proinflammatory protein expression, which was similarly abrogated by TGF-β inhibition. Finally, secretome profiling revealed an upregulation of inflammatory mediators in VCP mutant astrocyte conditioned media, and increased motor neuron apoptosis was rescued when TGF-β was inhibited in VCP mutant astrocytes. Together, our analysis reveals that human VCP mutant astrocytes feature dysregulated cell-autonomous reactive sub-states, driven by TGF-β activation, which partially recapitulate astrocyte dysregulation identified in patient postmortem single-cell studies. Inhibiting TGF-β rescues dysregulated VCP mutant sub-states and astrocyte-mediated neurotoxicity. These results collectively indicate that selective TGF-β pathway inhibition in astrocytes may be a potential therapeutic approach for ALS.

  单细胞
• Transmural Single-Nucleus Transcriptomics Nominates Candidate Disease Programs in Human Necrotizing Enterocolitis
  GSE351352Homo sapiens10 个样本2026-10-26

  Necrotizing enterocolitis (NEC) is a life-threatening disease of premature infants marked by inflammation, ischemia, mucosal injury, and, in advanced cases, necrosis extending into deeper layers of the intestinal wall. Because NEC affects specialized, interacting cells in a developing intestine, we used single-nucleus transcriptomics to build a transmural, cell-type-resolved map and nominate hypothesis-generating disease programs distinct from maturation. Full-thickness intestinal specimens from fetal/prenatal controls, acute NEC cases, and infant controls were analyzed by single-nucleus RNA sequencing (snRNA-seq). Fetal and infant samples served as developmental references. Analyses included cell annotation, NEC-versus-infant differential expression, gene ontology (GO), cross-lineage recurrence, cell-death signatures, and developmental maturity. We profiled 53,735 nuclei by snRNA-seq and resolved 34 epithelial, stromal, vascular, immune, neuronal, glial, and smooth-muscle populations. We used a morphology-based nuclei scoring system for sample selection that predicted high-quality transcript recovery. NEC nuclei were represented across this cellular landscape, with recurrent gene-expression changes suggesting shared inflammatory recruitment, antimicrobial/redox defense, stress adaptation, complement/vascular activation, reduced homeostatic signaling, and cell-death-associated regulation. Developmental maturity analysis identified fetal-like expression levels in subsets of NEC-regulated genes. Proliferative crypt populations retained DNA-repair/cell-cycle programs with inflammatory, hypoxic, and ER-stress features, while absorptive enterocytes showed reduced digestive, transport, detoxification, and terminal villus-function programs. Secretory-lineage changes implicated goblet mucus-barrier responses with reduced glycosylation, trafficking, and hydration; enteroendocrine changes in epithelial defense, metabolic stress, and neural signaling; and Paneth cell retention of antimicrobial effector transcripts despite altered ER quality control, autophagy, and granule delivery in NEC. Non-epithelial programs implicated stromal Wnt/BMP niche loss, impaired lymphatic drainage/scavenging, macrophage cytokine activation with reduced clearance machinery, neuroglial circuit defects, and altered smooth-muscle contraction-relaxation balance. This single nuclear intestinal cell atlas nominates multicellular programs that may govern NEC initiation, progression toward tissue destruction, and resolution toward functional recovery.

  单细胞细胞图谱
• Recordanelles for transcriptome-wide single-cell RNA recording in human cells [dataset_2 RNA-Seq]
  GSE344934Homo sapiens48 个样本2026-10-26

  Transcriptomic measurement technologies provide powerful approaches to understand biology but are limited to providing either a high-resolution snapshot at a moment in time or a low-resolution history of transcription constrained to a few genes over a narrow time range. Here, we introduce the “recordanelle”, a single-component synthetic organelle capable of recording the transcriptome in human cells. Recordanelles are composed of a mitochondrial membrane anchor, a condensate assembler and a poly-A-binding protein. We demonstrate that the recordanelle can be engineered to recruit engineered RNAs or a sampling of up to 90% of all endogenous mRNAs and protect them over several days. We further show that transient and dynamic transcriptional responses resulting from inducible promoters or interferon signaling are preserved throughout time within the recordanelle at the single-cell level. This work provides a non-disruptive and unbiased transcriptome-wide single-cell RNA recording technology to enable a deeper understanding of biology.

  单细胞
• Effect of TNFR2 agonism on CD4+ T cells (single-cell level) from healthy and SLE donors
  GSE344526Homo sapiens35 个样本2026-10-26

  We treated peripheral blood mononuclear cells from healthy donors and systemic lupus erythematosus (SLE) patients with (i) a human-specific tetravalent VHH-Fc fusion TNFR2 agonist, (ii) isotope control VHH and (iii) an IL2-mutein.

  单细胞
• Effect of TNFR2 agonism on human regulatory T cells
  GSE339300Homo sapiens10 个样本2026-10-26

  We isolated CD45RA+ Treg cells from human peripheral blood and treated them in vitro using a human TNFR2 agonist or a control VHH.
• Spatially Decoding Interactypes of Vascular and Synaptic Remodeling in the Glioblastoma Tumor Microenvironment by Surprisal Information-Theoretic Analysis
  GSE317289Homo sapiens10 个样本2026-10-26

  Glioblastoma (GBM) is a highly heterogeneous and invasive brain cancer, where interactions between tumor cells, vasculature, and neurons shape disease progression and therapeutic resistance. To better understand the spatial organization of these processes, we profiled ten tumor samples from five patients, one sample from T1-constrast-enhanced and one from non-contrast enhanced regions using spatial transcriptomic sequencing and multiplexed protein imaging. While each patient’s tumor presents a unique landscape, together these samples capture all major histological and spatial niches of GBM, enabling a complete picture of the tumor microenvironment and cell–cell “interactypes.” By applying surprisal analysis, an information-theoretic framework, for the first time to spatial omics data, we decomposed gene expression into orthogonal constraint modes that uncovered distinct processes such as extracellular matrix remodeling, vascular-associated invasion, and neuron–tumor synaptic interactions, each with well-defined molecular mechanism. Complementing this approach, a spatial ligand–receptor interactype analysis mapped specific communication events across niches. Within the perivascular niche, we observed collagen–integrin signaling linked to a trajectory from astrocyte-like to mesenchymal-like tumor states. At neuron–tumor interfaces, synaptic remodeling emerged, characterized by NLGN1–NRXN1 and SEMA5A–MET interactions together with enrichment of neuronal gene modules including MAP2 and CALM1. These findings suggest that surprisal analysis can reveal vascular remodeling and neuron-tumor crosstalk are critical mechanisms of GBM progression. This study demonstrates the use of surprisal information-theoretic analysis of spatial omics data to expose hidden spatial programs with mechanistic insights and the interactype mapping to decode the GBM biology across all major tumor niches, pointing toward the discovery of potential therapeutic vulnerabilities mediated by cell-cell interaction and microenvironments.

  空间转录组