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。

• GOLDEN: Gene expression and allele-informed decomposition for genetic heterogeneity in spatial transcriptomic data
  GSE341398Homo sapiens2 个样本2026-10-31

  Spatial transcriptomics (ST) enables exploration of cellular interactions, but current methods rely on pathologist annotation and face limitations in addressing genetic heterogeneity, where niches harbor non-clonal cells, as in placental or allograft tissues. To decipher such inter-individual heterogeneity in ST, we developed GOLDEN (Gene expression and allele-informed decomposition for genetic heterogeneity), an allele-aware multi-task network that encodes spot-level expression into shared latent representations. Incorporating allele features, it uses dual heads to classify spot identity (target, non-target, or mixed) and to estimate target fractions. For evaluation, we generated synthetic ST data via a Gamma-distribution model using semi-allogeneic single-cell profiles. On these synthetic benchmarks, GOLDEN achieved reliable deconvolution (Pearson's r = 0.977; MAE = 0.045) while maintaining consistent predictions across real-world STs, which were validated through genetic evidence.

  单细胞空间转录组计算与 AI
• The transcriptomic profile of wild-type HGC-27 cells treated with conditioned media from ANGPTL4-overexpressing or control HGC-27 cells
  GSE338826Homo sapiens4 个样本2026-10-31

  Given that ANGPTL4 is a secreted protein, we combined conditioned medium treatment with transcriptomic analysis to determine whether the activation of downstream signaling pathways by ANGPTL4 overexpression is dependent on its secretion.
• 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.
• Single-cell atlas reveals shared early microenvironmental remodeling in colorectal polypogenesis
  GSE327909Homo sapiens6 个样本2026-10-31

  Colorectal polyps are the earliest precancerous lesions in colorectal carcinogenesis, but their common microenvironmental drivers remain incompletely defined. We performed single-cell RNA sequencing on paired normal mucosal and colorectal polyp tissues from 3 patients with unselected lesions, including hyperplastic polyps and tubular adenomas. After quality control, 31,147 high-quality cells were obtained. Comparative analysis revealed four conserved hallmarks of colorectal polyps relative to normal mucosa: disrupted epithelial homeostasis characterized by stem cell expansion, Paneth cell reduction, and Wnt pathway activation; pro-inflammatory polarization of CD4+ T cells with increased Th17 cells and activation of NF-kB/IL-17-related pathways; functional reprogramming of CD8+ T cell subsets, especially decreased IELs with specialized immune functions; and extensive remodeling of immune-epithelial intercellular communication, including CD55-ADGRE5, MIF-CD74, and GZMA-PARD3 signaling axes. These data provide a single-cell atlas of shared microenvironmental changes in early colorectal polypogenesis.

  单细胞细胞图谱
• A Single-Cell Atlas of Human Periodontal Ligament During Orthodontic Tooth Movement
  GSE327337Homo sapiens5 个样本2026-10-31

  Orthodontic tooth movement (OTM) requires coordinated remodeling of the periodontal ligament (PDL) and alveolar bone, yet the cellular architecture underlying this process in human tissues remains incompletely understood. Here, we generated the first single-cell transcriptomic atlas of the human PDL during OTM by profiling cells from the pressure and tension sides of teeth collected at day 3 and day 7 following force application. This atlas reveals the major stromal and immune cell populations and highlights spatial and temporal heterogeneity across force conditions and remodeling stages.

  单细胞空间转录组细胞图谱
• 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.
• Upregulated TRPM1 is associated with apoptosis in Rs1 knockout mice and in ARPE19 cells through increased intracellular calcium
  GSE326551Homo sapiens8 个样本2026-10-31

  The pathological mechanism underlying retinal apoptosis in X-linked retinoschisis (XLRS), a disease caused by retinoschisin 1 (RS1) deficiency, remains incompletely understood. This study aimed to investigate the role of transient receptor potential melastatin 1 (TRPM1) in retinal tissues and cells. Retinal function and structure were assessed by electroretinography (ERG) and optical coherence tomography (OCT). Protein expression was evaluated by immunofluorescence staining and western blotting (WB). Retinal morphology was examined by hematoxylin and eosin (H&E) staining. Apoptotic retinal cells were detected by TUNEL staining. Key proteins were screened using proteomics data obtained by mass spectrometry. Intracellular calcium levels were measured using Rhod-2 AM. TRPM1 expression in Rs1-KO mice was 1.3-fold higher than that in wild-type mice (p < 0.05), whereas TRPM1-overexpressing ARPE19 cells exhibited approximately twofold higher expression than the empty vector control group. Mechanistically, TRPM1-mediated calcium influx promoted calcium/calmodulin-dependent protein kinase II (CAMKII) phosphorylation. Concomitantly, the accumulation of the autophagy-related proteins P62 and LC3B, increased BAX expression, and decreased BCL2 expression were observed in both Rs1-KO retinal tissues and TRPM1-overexpressing ARPE19 cells. These findings collectively suggest that TRPM1 may contribute to cell’s apoptosis. Our study provides new insight into the mechanism of retinal apoptosis in XLRS.
• Somatic TP53 Mutations Drive T and NK Cell Dysfunction and Create an Inflammatory Immune Niche in Acute Myeloid Leukemia
  GSE324592Homo sapiens2 个样本2026-10-31

  TP53-mutant acute myeloid leukemia (AML) is characterized by poor prognosis and limited response to immunotherapy, yet the mechanisms underlying immune failure in this setting remain unclear. Here, we integrate single-cell DNA sequencing with surface proteomics to demonstrate that somatic TP53 mutations arise not only in leukemic blasts but also in T and NK cells from patients with TP53-mutant AML. TP53-mutant T cells exhibit enhanced exhaustion phenotypes, impaired cytotoxic function, and altered clonal architecture. Mechanistically, mutant p53 reprograms T cells toward a pro-inflammatory yet dysfunctional state, reshaping cytokine networks and promoting a niche enriched in inflammatory and myeloid-supportive signals. These mutant T cells impair both intrinsic effector function and the functionality of surrounding immune cells. Introduction of TP53 mutations into healthy donor T cells recapitulates exhaustion and impaired tumor control, whereas elimination of mutant p53 restores effector function, normalizes cytokine programs, and improves disease control in a TP53-mutant AML xenograft model.

  单细胞
• Enhanced plasmin generation due to PAI-1 deficiency impairs regulated vascular endothelial cell motility.
  GSE320323Homo sapiens6 个样本2026-10-31

  Background: Plasminogen activator inhibitor-1 (PAI-1) plays a crucial role in the plasminogen activation system and fibrinolysis. Congenital PAI-1 deficiency in humans is characterized by severe bleeding and delayed wound healing, which is consistent with the altered regulation of the fibrinolytic regulation. Although plasmin influences various cellular processes, the mechanisms by which PAI-1-mediated control of plasminogen activation and regulates endothelial cell (EC) behavior, especially at the pericellular level, are not well understood. The aim of this study was to elucidate the specific cellular effects of enhanced plasminogen activator (PA) activity caused by PAI-1 deficiency in human ECs. Methods: PAI-1 deficient human ECs (PAIKO-ECs) were generated using CRISPR/Cas9-mediated gene editing and compared them with wild-type ECs (WT-ECs). We investigated the impact of plasminogen-induced pericellular plasmin activity and its impact on endothelial migration and angiogenic tube formation, conducting additional transcriptomic analysis. Results: PAIKO-ECs exhibited markedly increased PA activity, as demonstrated by elevated plasmin generation in the presence of plasminogen. In scratch assays, PAIKO-ECs exhibited increased overall uncoordinated motility with multidirectional migration trajectories and impaired directional wound closure in the presence of plasminogen; however, cell proliferation remained unaffected. This aberrant migratory phenotype was reversed by aprotinin, recombinant active PAI-1, or the lysine analog epsilon-aminocaproic acid (EACA). EACA notably reduced plasminogen accumulation on the cell surface while preserving fluid-phase plasmin generation. This indicates that enhanced EC motility is driven by pericellular rather than fluid-phase plasmin activity. In tube formation assays, PAIKO-ECs formed a higher number of extremities and branches, a phenotype that was reversed to the level of WT-ECs by EACA or aprotinin. Transcriptome analyses revealed differential gene expression related to fibrinolysis, angiogenesis, and endothelial-mesenchymal transition. Conclusions: These findings reveal that pericellular plasmin activity is essential for EC motility and angiogenic behavior under PAI-1-deficient conditions. This provides novel mechanistic insight into the spatial plasminogen activation systems in vascular remodeling.

  空间转录组
• 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.
• ReprogRAM nanoplatform for direct conversion of fibroblasts into reprogrammed osteoblasts for bone regeneration
  GSE315875Homo sapiens4 个样本2026-10-31

  mRNA-based direct conversion offers an integration-free route for osteogenic cell-fate reprogramming, yet efficient reprogramming typically requires sustained expression of reprogramming factors. Here, we develop ReprogRAMs (Reprogrammable RNA Assemblies for Multi-factor expression), a self-assembled concatemeric mRNA nanoparticles synthesized by rolling-circle transcription and engineered for cap-independent translation. A single delivery of ReprogRAM to human dermal fibroblasts enabled cytosolic expression that persisted over time with minimal cytokine induction. By leveraging this long-acting expression profile, we encoded the osteogenic reprogramming factors Oct4 and Cbfβ and implemented a hybridized delivery strategy to enforce co-expression of both factors. ReprogRAM induced robust osteogenic conversion, as evidenced by increased mineralized matrix deposition, induction of osteoblast markers, and transcriptomic remodeling toward osteoblasts. Finally, transplantation of ReprogRAM-derived reprogrammed osteoblasts (rOBs) embedded in a gelatin scaffolds promoted bone repair in a critical-sized mouse calvarial defect model. Together, ReprogRAM provides a long-acting, integration-free mRNA modality for in situ cell-fate engineering and bone regeneration.
• 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
  GSE280503Homo sapiens6 个样本2026-10-31

  In this study, transient transcriptome sequencing (TT-seq) was performed to dectect the impact of the overexpression of CTCF-s on nascent RNA and antisense RNA.
• BL-Hi-C, Deciphering the diversities of CTCF and CTCF-s in human embryonic stem cells
  GSE280419Homo sapiens8 个样本2026-10-31

  In this study, we performed BL-Hi-C to investigate the influence of the expression of CTCF/CTCF-s on higher-order chromatin structures.
• 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.