GEO 数据集

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

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

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

  空间转录组
• 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.
• 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.
• 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.
• 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.
• 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.
• Single-cell analysis reveals transcriptomic patterns in active macrophage activation syndrome and therapeutic potential of albumin-fused interleukin-10 in a mouse model
  GSE331089Homo sapiens20 个样本2026-10-31

  Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperinflammatory conditions characterized by excessive immune activation and cytokine production. To clarify immune cell characteristics and identify potential therapeutic targets in MAS, we performed single-cell RNA sequencing (scRNA-seq) on bone marrow and peripheral blood samples from patients with newly developed MAS caused by diverse etiologies. To broaden the current knowledge of the immune landscape in the bone marrow, we performed scRNA-Seq of bone marrow cells and isolated blood leukocytes obtained from MAS patients using the Seq-Well.

  单细胞
• MUC13 enhances IL-17 signaling pathway activity in nasal epithelial cells
  GSE329876Homo sapiens12 个样本2026-10-31

  MUC13 is a membrane-bound mucin involved in epithelial protection and barrier maintenance, but its role in nasal epithelial inflammation remains unclear. This study aimed to investigate the function of MUC13 in nasal epithelial cells (NECs) and its potential involvement in inflammatory signaling. Primary NECs were isolated from patient-derived inferior turbinate mucosa, and MUC13 overexpression was established by direct transfection of human MUC13 mRNA. RNA sequencing and bioinformatics analyses were performed to characterize transcriptomic changes.
• Endogenous PD-L1-Blocking Antibodies Drive Potent Anti-Tumor Immunity
  GSE326633Homo sapiens27 个样本2026-10-31

  Checkpoint blockade therapy, though transformative, remains ineffective in 70-80% of patients, with autoimmune adverse effects. Here, we provide the first evidence of a naturally occurring form of immune checkpoint blockade mediated by endogenous antibodies that functionally replicate the effects of therapeutic checkpoint inhibitors, without autoimmune symptoms. Through cloning and reconstructing patient-derived monoclonal antibodies, we show that certain cancer patients produce PD-L1-blocking antibodies that can restore T cell function and induce potent anti-tumor immunity. Broad polyreactive responses to multiple checkpoints confer no survival advantage. However, patients who are selectively positive for PD-L1 antibodies exhibit prolonged survival, tumors enriched with memory T cells, and activated circulating T cells. Mechanistically, these PD-L1 antibodies block PD-1/PD-L1 interactions and restore T cell function, in vitro and in vivo, revealing a naturally regulated form of checkpoint inhibition. Our data reveal that key principles of successful immunotherapy can emerge endogenously in a subset of patients, redefining our understanding of immune competence, tolerance, and therapeutic responsiveness in cancer, offering a mechanistic framework to explain how certain patients mount more effective anti-tumor immunity.
• Comparative profiling of SARS-CoV-2 variant infections reveals diverse impacts on host cell RNA and RNA binding protein distribution and regulation
  GSE318110Homo sapiens14 个样本2026-10-31

  RNA viruses perturb cellular RNA metabolism to promote viral transcript expression and genome replication. However, the extent of host cell RNA reprogramming and the consequences on RNA binding protein (RBP) expression and localization remain poorly understood. Here, we utilized an integrated set of transcriptomics, proteomics, and high-content imaging approaches to compare the impact of different SARS-CoV-2 variants, including an early viral isolate and later emerging variants of concern (Alpha, Delta and Omicron) on the host cellular RNA and RBP landscapes. While all variants deeply remodelled the host transcriptome in a subcellular compartment-specific manner, we found that Omicron variants express lower levels of viral RNA products compared to earlier variants, while still driving efficient production of viral proteins. The surge in viral RNA expression correlated with altered subcellular RNA biotype distribution, cytoplasmic mRNA exclusion, the selective disruption of the localization of polyA-tail interacting proteins, and the nuclear accumulation of non-coding transcripts such as RN7SL family members and MALAT-1. Unexpectedly, we found many RBPs that exhibiting altered subcellular localization following abiotic innate immune stimulation with poly(I:C) but remained unaltered in cells infected with SARS-CoV-2 variants, revealing a capacity for these viruses to limit the overall impact on the RBP subcellular distribution. Our results further indicate that Omicron infection sustains higher expression levels of proteins components of the signal recognition particle and translation factors, which may enable a more effective production of immune response and viral components. Altogether, this work highlights the deep impact of SARS-CoV-2 infection on host cell RNA regulatory landscape and provides new insights to explain the differential impact of Omicron compared to early SARS-CoV-2 variants.

  扰动筛选
• Regenerative macrophages from human iPSCs promoted vascular remodeling in human atherosclerotic organoid model
  GSE317284Homo sapiens26 个样本2026-10-31

  Recent studies have revealed that macrophages exhibit greater phenotypic diversity than the traditional M1/M2 classification, enabling them to display distinct functional properties depending on the surrounding microenvironment. Accordingly, it has become increasingly important to more finely characterize and evaluate macrophage subtypes that may operate within specific disease microenvironments. In this study, we aimed to identify a macrophage phenotype with therapeutic potential for atherosclerosis using an atherosclerosis-induced blood vessel organoid (BVO) model. To assess the effects of diverse macrophage phenotypes on the atherosclerosis, iPSC-derived macrophages (iMac) were generated and polarized into multiple phenotypic states. The polarized iMac populations displayed distinct gene expression profiles and exhibited functional differences in angiogenesis and regeneration related assays. For therapeutic evaluation, iPSC-derived BVOs were established and then induced to develop atherosclerotic features. During co-culture with the atherosclerotic BVO model, iPSC-derived regenerative macrophages (iMac R) showed active interactions with the organoids and produced therapeutic benefits on lipid clearance, anti-inflammatory responses, and regenerative effects. Notably, iMac R demonstrated superior therapeutic efficacy compared with other polarized macrophage phenotypes, highlighting their potential as a novel cell-based therapeutic strategy for atherosclerosis.
• CRISPR screen after venetoclax and azacitidine treatment in AML cells
  GSE314297Homo sapiens12 个样本2026-10-31

  CRISPR screen was performed in three isogenic MOLM-13 acute myeloid leukemia (AML) cell lines (p53 WT/p53 R248Q/p53 KO) to analyze gene dependencies changes after treatment with venetoclax and azacitidine.

  扰动筛选
• Accurate In Vitro Recapitulation of Bile and Blood Partitioning of Drug Metabolites Using a hepatocyte culture system with induced open-form bile canaliculus icHep
  GSE307757Homo sapiens16 个样本2026-10-31

  Systemically circulating drug metabolites can cause organ damage, and there are species differences in the both the types of metabolites formed and their partitioning into bile and blood. Thus, it is necessary to evaluate the formation and biliary excretion of hepatic drug metabolites using in vitro evaluation system using human hepatocytes. Conventional sandwich-cultured hepatocytes (SCHs), however, form closed bile canaliculi that preclude direct collection of biliary excreted metabolites. Here, we assessed whether primary cultured hepatocytes with induced open-form bile canaliculus (icHep) provide a suitable system for evaluating the partitioning of drug metabolites produced in hepatocytes between bile and blood. Human hepatocytes derived from human liver–chimeric mice were cultured on claudin-1–coated plates, which facilitated the formation of open bile canalicular lumina, confirmed by co-immunostaining for MRP2 and ZO-1. RNA-seq analysis revealed that the expression levels of representative pharmacokinetics-related genes in icHep were comparable to those in SCHs. Following the addition of parent drugs to the blood-side chamber, metabolites were successfully collected from both blood- and bile-side chambers. Ziprasidone sulfoxide and mycophenolic acid glucuronide were predominantly recovered on the blood side, whereas celecoxib carboxylic acid and SN-38 glucuronide were preferentially excreted into bile. The metabolite partitioning observed in icHep was consistent with human in vivo data. In conclusion, icHep enables a quantitative evaluation of the hepatic disposition of drug metabolites including partitioning into bile and blood in human and represents a physiologically relevant in vitro system for human pharmacokinetic studies.
• Transcriptomic changes from resulting from treatment of SVG-A with drugs of abuse
  GSE306251Homo sapiens21 个样本2026-10-31

  SVG-A cells were treated with drugs of abuse (ethanol, cocaine, morphine, THC, and psilocin) prior to RNA sequencing. A bioinformatics pipeline of Trim Galore, Kallisto, DESeq2 and Qiagen Ingenuity Pathway Analysis was used for pathway analysis.
• Disruption of nucleolar integrity triggers cellular quiescence through organelle rewiring and secretion
  GSE305361Homo sapiens27 个样本2026-10-31

  Intrinsic cellular stress responses are often mis regulated in complex human diseases such as cancer and neurodegeneration. To investigate how cellular homeostasis is balanced upon loss of key membraneless organelle – Nucleolus, we performed unbiased systems approach including cellular and temporal characterization of activated cellular stress signaling, associated sub-cellular changes and changes in cellular states and behavior. We report that transient loss of nucleolar architecture and defective ribosome biogenesis is well tolerated by cells as they undergo prolonged cell cycle arrest and rely on buffering capacity of cytoplasmic translation machinery. Cells immediately mount a comprehensive stress response predominantly mediated by TP53 and its downstream effector proteins. This mounted stress response is distinct from other acute stresses altering nucleolar morphology or function such as Pol I inhibition by ActD, heat shock or chemicals like Arsenate and CPT. Cells show a robust transcriptional reprogramming showing upregulation of structural and signaling genes of organelles such as Golgi apparatus and Endo-lysosomal vesicles. This leads to translation and microscopically evident tubular-vesicular expansion of Golgi and increase in number and size of endo-lysosomes. Cells become secretory, pro-metastatic and alter their cell-to-cell communication behavior. Taken together, these stress response pathways show an adaptive quiescent program and acquired partial EMT, allowing cells to resist loss of ribosome biogenesis, nucleolar architecture and ensure survival and restore homeostasis upon recovery. Correlatively, similar stress adaptions are seen to be contributing to progression of different cancer types especially in breast cancer and AML originating in the later stages of ribosomopathies.
• scRNA-seq of skin and PBMC samples of systemic sclerosis patients and healthy controls
  GSE299141Homo sapiens20 个样本2026-10-31

  Skin and blood samples from systemic sclerosis (SSc) patients and healthy donors were analyzed using single-cell transcriptomics (scRNA-seq). CCL19+ fibroblast was upregulated in the dermis of patients with SSc, and exhibited high expression of immuno-regulatory genes, including CCL19. CCL19 expression correlated with the severity of dermal fibrosis in SSc. The most significant ligand-receptor interaction from CCL19+ fibroblast to T cells in SSc skin was CCL19-CCR7. Furthermore, CCR7+ T cells in the fibrotic skin, particularly CCR7+CD8+ T cells, displayed enhanced stemness and cytotoxicity, actively interacting with extracellular matrix (ECM)-producing fibroblasts in SSc.

  单细胞
• SUMOylation of SND1 promotes degradation of novel tumor suppressive miRNAs in cancer cells
  GSE281560Homo sapiens16 个样本2026-10-31

  Endonuclease Staphylococcal nuclease domain-containing protein 1 (SND1) was reported mediate miRNA decay of both protein-free and AGO2-loaded miRNAs. We recently found that SUMOylation of SND1 is involved in the regulation of the mature miRNA decay. The in vivo and in vitro SUMOylation assay have proven that SND1 can be modified by SUMO1 at the major site K513, and this modification can be enhanced upon the sodium arsenite and heat shock. Mutation K513R of SND1 inhibits cell proliferation and colony formation of H1299 cells under both normal and sodium arsenite stimulated conditions. Our data demonstrate that miRNA metabolism is connected to cellular stress response and tumorigenesis through the reversible SUMOylation of SND1. The stress-induced SND1 SUMOylation can degrade miRNA to regulate mRNA homeostasis, which may be a key node in the stress survival strategy.
• Deciphering the diversities of CTCF and CTCF-s in human embryonic stem cells [ChIP-seq]
  GSE280302Homo sapiens11 个样本2026-10-31

  In this study, Biotin ChIP-seq was performed to obtain the independent genome binding sites of CTCF-s or CTCF. CTCF ChIP-seq was performed to investigate the influence of the overexpression of CTCF-s on the binding of CTCF in hESCs.
• Habitual betel nut chewing promotes oral squamous cell carcinoma tumorigenesis by inhibiting global methylation in normal oral mucosa
  GSE280233Homo sapiens33 个样本2026-10-31

  Oral squamous cell carcinoma (OSCC) is a major oral-maxillofacial tumor with marked effects on facial appearance and high recurrence rate. In addition to tobacco and alcohol consumption, betel nut chewing plays a significant role in promoting the occurrence of OSCC, highlighted by the prevalence of oral cancer in East Asia, Southeast Asia, and South Asia. However, the specific underlying mechanisms are unclear. By analyzing clinical data, we first noted that habitual betel nut chewing only affect occurrence of second primary tumors, indicated that it induces tumorigenic changes in the normal tumor-adjacent mucosa tissues. Tumorigenesis relies on the combined effect of genetic and environmental changes, with epigenetic changes, primarily methylation, serving as a key link connecting genetics and the environment. Herein, we analyzed global DNA methylation in the oral mucosa and found that habitual betel nut chewing leads to significant hypomethylation in the normal tumor-adjacent mucosa. This change makes the normal mucosa more similar to OSCC tissues than other normal tissues at the molecular pathological level. Our multiomics analysis revealed that habitual betel nut chewing may facilitate tumorigenesis by reducing the global DNA methylation level of normal mucosa, suppressing antitumor immunity, and promoting abnormal cell proliferation. Through experimental verification and screening, we identified five key genes involved in this process: DEPDC1B, ANLN, ECT2, SPC25, and PLK1. Our study revealed that habitual betel nut chewing can promote OSCC tumorigenesis by regulating global DNA methylation. Early detection of global DNA methylation and key gene markers may reveal potential targets for assessing OSCC risk.

  多组学
• Joint profiling of 5-methylcytosine, 5-hydroxymethylcytosine, and the transcriptome in single cells identifies factors responsible for genome-wide DNA methylation erasure in human primordial germ cell maturation
  GSE280112Homo sapiens23 个样本2026-10-31

  Reprogramming of DNA methylation plays a vital role in the establishment of cell identity during early mammalian development. To gain deeper mechanistic insights into this process requires capturing the entire dynamics of DNA methylation – both 5-methylcytosine (5mC) and its downstream oxidation product 5-hydroxymethylcytosine (5hmC) – in individual cells. Therefore, in this work, we report a new single-cell genome-wide strand-specific sequencing method, scMHT-seq, to jointly profile 5mC, 5hmC, and the transcriptome from individual cells. Using human embryonic stem cells (hESCs), we first show that scMHT-seq can accurately detect both 5mC and 5hmC from the same cell with minimal crosstalk in quantifying these two DNA modifications, and that the multi-modal measurements are in close agreement with individual measurements of 5mC and 5hmC in single cells. After establishing scMHT-seq, we next applied scMHT-seq to gain insights into human primordial germ cell (hPGC) maturation. After specification, hPGCs undergo rapid global demethylation as they mature, and this reprogramming is critical for normal development of gametes. However, it has not been possible to overcome this key epigenetic barrier in a dish, thereby limiting our ability to generate mature hPGC-like cells (hPGCLCs) and accomplish in vitro gametogenesis. To gain a deeper understanding of the molecular factors involved in germ cell maturation, we applied scMHT-seq to an extended in vitro culture system for generating hPGCLCs and observed partial and heterogeneous erasure of the methylome across single cells that is mechanistically predominantly driven by passive demethylation due to reduced DNMT1-mediated maintenance methylation activity. Notably, we discover that hPGCLCs in extended culture can be transcriptionally classified into two distinct states, with one population enriched for more mature hPGCLCs exhibiting genome-wide loss of the methylome. Moreover, we identify DND1 and SOX15 as two critical factors that are potentially key drivers of hPGCLC maturation. Overall, we demonstrate that scMHT-seq is a robust and high-throughput technology that can provide insights into the mechanisms driving DNA methylation dynamics and their effect on cellular states during hPGCLC maturation, thereby providing a platform to advance in vitro gametogenesis in humans.

  单细胞
• Type I regulatory T cells have overlapping phenotypes with circulating Tfh and Th1 in P. falciparum
  GSE279685Homo sapiens16 个样本2026-10-31

  Immunity to P. falciparum malaria develops slowly, requiring repeated infection in areas of high transmission, and wanes rapidly in the absence of parasite exposure. Key to this immunity, is the development of antibodies which is supported by CD4⁺ T follicular helper (Tfh) cells that drive robust germinal centre responses. However, in malaria, the malaria-specific CD4⁺ T cell compartment in peripheral blood is dominated by Type 1 regulatory T cells (Tr1), which produce high levels of IL-10 in response to parasites. Tr1-like Tfh cells (Tfh10) have been reported in several settings of repeated antigen stimulation but have not been investigated in malaria. Here we used single-cell RNA sequencing and multiparameter flow cytometry to characterise malaria-specific Tfh and Tr1 cells in a longitudinal cohort of highly exposed individuals and assessed their persistence after transmission interruption. Malaria-specific Tfh and Tr1 cells shared overlapping profiles, and Tr1 cell-like transcriptional signatures and phenotypes were detectable within the Tfh cell compartment. Tfh10 cell subsets were the dominant phenotype of malaria-specific Tfh cells. Following disruption of malaria transmission, the frequencies of malaria-specific Tr1 and Tfh10 cells declined. These findings highlight a close relationship between Tfh and Tr1 cells and show that the Tfh cell compartment in malaria is dominated by Tfh10 cells. The rapid waning of these cells in the absence of continuous exposure is consistent with requirements of persistent antigen in maintaining regulatory CD4 T cell phenotypes.

  单细胞
• Collection of CRC cell line grown in vitro
  GSE271191Homo sapiens19 个样本2026-10-31

  Recent studies revealed the presence of an aggressive subgroup of colorectal cancer (CRC) that exhibits a distinct tumor growth pattern, characterized by high abundance of cancer-associated fibroblasts (CAFs). To identify cancer cells-intrinsic traits underlie this phenotype and to characterize its stromal features, we generated mouse xenografts from 19 CRC cell lines, where normal mouse stroma cells are recruited and educated by epithelial cancer cells. The in vivo xenograft growth rate showed high variability between cell lines, revealing a subgroup of slow-paced tumors. Cancer cells of this subgroup display distinctive transcriptional features, only partially captured by previously described CRC molecular subtypes, involving epithelial-mesenchymal transition and cooperation with a specific CAF population in remodeling the extracellular matrix. We therefore called the cancer cell signature “epithelial matrix remodeling” (EMR), and the CAF signature “matrix remodeling CAF” (mrCAF). In pan-cancer analysis, the EMR and mrCAF signatures were co-detected and associated with poor prognosis in multiple tumor types. Altogether, these results highlight the intrinsic capability of cancer cells to recruit, educate and cooperate with CAFs, indicating route toward tumor progression involving the interaction between tumor and its microenvironment.
• Collection of CRC cell line grown in vivo
  GSE267353Homo sapiens38 个样本2026-10-31

  Recent studies revealed the presence of an aggressive subgroup of colorectal cancer (CRC) that exhibits a distinct tumor growth pattern, characterized by high abundance of cancer-associated fibroblasts (CAFs). To identify cancer cells-intrinsic traits underlie this phenotype and to characterize its stromal features, we generated mouse xenografts from 19 CRC cell lines, where normal mouse stroma cells are recruited and educated by epithelial cancer cells. The in vivo xenograft growth rate showed high variability between cell lines, revealing a subgroup of slow-paced tumors. Cancer cells of this subgroup display distinctive transcriptional features, only partially captured by previously described CRC molecular subtypes, involving epithelial-mesenchymal transition and cooperation with a specific CAF population in remodeling the extracellular matrix. We therefore called the cancer cell signature “epithelial matrix remodeling” (EMR), and the CAF signature “matrix remodeling CAF” (mrCAF). In pan-cancer analysis, the EMR and mrCAF signatures were co-detected and associated with poor prognosis in multiple tumor types. Altogether, these results highlight the intrinsic capability of cancer cells to recruit, educate and cooperate with CAFs, indicating route toward tumor progression involving the interaction between tumor and its microenvironment.
• Transcriptomic changes from resulting from treatment of KNS42 with drugs of abuse
  GSE246989Homo sapiens28 个样本2026-10-31

  KNS42 cells were treated with drugs of abuse (ethanol, cocaine, morphine, THC, and psilocin) prior to RNA sequencing. A bioinformatics pipeline of Trim Galore, Kallisto, DESeq2 and Qiagen Ingenuity Pathway Analysis was used for pathway analysis.
• ISL1 and AQP5 complement each other to enhance gastric cancer cell stemness by regulating CD44 expression
  GSE246329Homo sapiens12 个样本2026-10-31

  Gastric cancer, a prevalent and life-threatening malignancy, is believed to involve cancer stem cells as a contributing factor to tumor progression. This study delves into the influence of ISL1 on the stem-like properties of human gastric cancer cells. In human gastric cancer samples, there is an observed elevation in ISL1 expression, which correlates with the expression of stem cell markers, notably LGR5. Functionally, ISL1 fosters the self-renewal, cell proliferation, migration, and the clonogenic potential of gastric cancer cells in vitro. Furthermore, it enhances the ability of these cells to form tumors and metastasize in vivo. Additionally, ISL1 collaborates with AQP5, collectively intensifying the tumorigenicity of gastric cancer cells. Mechanistically, transcriptomic analysis of cells overexpressing ISL1 unveils a notable activation of the FOXO pathway. This activation leads to increased nuclear expression of FOXO3, subsequently resulting in elevated expression of the stemness-associated gene CD44 in gastric cancer cells. These findings shed light on the role of ISL1 in promoting the stem-like characteristics of gastric cancer cells and emphasize the connection between ISL1 and AQP5 as a novel therapeutic target for individuals with gastric cancer.
• Genome-wide DNA methylation analysis in colorectal tumor and normal tissues
  GSE159670Homo sapiens24 个样本2026-10-31

  The current risk stratification system defined by clinicopathological features do not accurately identify the risk of disease recurrence in patients with stage I-II colorectal cancer (CRC). We aimed to investigate whether the CpG sites from newly established genome-wide methylation profiles could serve as biomarkers to improve prognosis prediction.
• Cilengitide limits the progression of both syndromic and sporadic thoracic aortic aneurysms by targeting alpha V integrins
  GSE352523Homo sapiens11 个样本2026-10-30

  Spatial transcriptomics was used to characterize gene expression patterns in human ascending aortic tissue from healthy controls, patients with Marfan syndrome (MFS), and patients with sporadic thoracic aortic aneurysm (sTAA). Carnoy-fixed, paraffin-embedded ascending aortic tissue sections were profiled using the 10x Genomics Visium platform. Spatially resolved gene expression profiles were analyzed to investigate transcriptional heterogeneity, pathway-associated signatures, and inferred cellular composition across disease groups.

  单细胞空间转录组
• T cell responses distinguish the subset of oral dysplasia that progressed to cancer
  GSE351967Homo sapiens16 个样本2026-10-30

  The factors that determine which oral premalignant lesions progress to cancer while others do not remain unclear. Immune responses to early lesions result in cancer immunoediting, so variability in their nature and strength may influence risk of cancer progression. Here, we show that T cell-mediated immune responses arise in oral premalignant dysplasia years before invasive cancer develops and distinguish lesions that progress from those that do not. Progressing lesions were characterized by robust infiltration of CXCL13+ CD8 T cells in proximity to dysplastic epithelial cells and macrophages expressing interferon-stimulated genes (ISGs), including the T cell-recruiting chemokines CXCL9, CXCL10, and CXCL11. Infiltrating CXCL13+ CD8 T cells were clonally expanded and persisted through malignant transformation. Over time, their frequency and transcriptional profile remained stable, while myeloid cells accumulated and basal epithelial cells upregulated an extracellular matrix-associated transcriptional program partly induced by IFNγ. The transition to invasive cancer was subsequently marked by tissue remodeling accompanied by a shift of the CXCL13+ CD8 T cells from the epithelium to the underlying stroma. Our results provide evidence that IFNγ-driven immune signatures are detectable early and distinguish progressing oral lesions.