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
• Baseline immune transcriptional states predict future HIV-1 acquisition in individuals at risk of sexual infection
  GSE352331Homo sapiens104 个样本2026-10-31

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

  空间转录组
• Spatial transcriptomic analysis of fibroblast therapy with collagen/PMMA in human skin [Xenium]
  GSE350895Homo sapiens3 个样本2026-10-31

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

  空间转录组
• Gene expression in pericental and periportal hepatocytes
  GSE349461Mus musculus4 个样本2026-10-31

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

  空间转录组
• 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
• Stereo-seq of aortic atherosclerotic lesions in common mouse models
  GSE331239Mus musculus3 个样本2026-10-31

  A spatial transcriptomic analysis of aortic root atherosclerotic lesions for a comparison between common mouse models of atherosclerosis

  空间转录组
• 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
• 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
• Spatial genome and transcriptome co-mapping reveals clonal heterogeneity in tumor tissue
  GSE276213Mus musculus; Homo sapiens22 个样本2026-10-31

  This SuperSeries is composed of the SubSeries listed below.

  空间转录组SuperSeries
• Spatial genome and transcriptome co-mapping reveals clonal heterogeneity in tumor tissue [DNA-Seq]
  GSE276212Homo sapiens; Mus musculus11 个样本2026-10-31

  Tumor heterogeneity arises from the sequential acquisition of somatic mutations and the selection of fitter clones, leading to distinct genotypes and phenotypes. Joint mapping of genome and transcriptome in the same tumor tissue can directly link clonoal relation to transcriptional state enabling a more in-depth understanding of intrinsic and extrinct tumor heterogeneity in the tissue context. Here, we introduce Spatial-GT-seq, a spatial multi-omic technology capable of genome-wide co-profiling of the genome and transcriptome at near single-cell resolution. We demonstrated in situ identification of tumor subclones in a mouse model of lung metastasis, with parallel transcriptomic profiles indicating that the gene expression profile of the same tumor clone is altered by the tumor microenvironment. Furthermore, analysis of primary and recurrent human pancreatic neuroendocrine tumors reveals both persistent and newly emerging tumor subclones, exhibiting transcriptional changes in both the original and recurrence sites. These findings highlight Spatial-GT-seq as a valuable platform for studying genotype-phenotype-microenvironment associations, providing new insights into cancer evolution and heterogeneity.

  单细胞空间转录组多组学
• Spatial genome and transcriptome co-mapping reveals clonal heterogeneity in tumor tissue [RNA-Seq]
  GSE276211Homo sapiens; Mus musculus11 个样本2026-10-31

  Tumor heterogeneity arises from the sequential acquisition of somatic mutations and the selection of fitter clones, leading to distinct genotypes and phenotypes. Joint mapping of genome and transcriptome in the same tumor tissue can directly link clonoal relation to transcriptional state enabling a more in-depth understanding of intrinsic and extrinct tumor heterogeneity in the tissue context. Here, we introduce Spatial-GT-seq, a spatial multi-omic technology capable of genome-wide co-profiling of the genome and transcriptome at near single-cell resolution. We demonstrated in situ identification of tumor subclones in a mouse model of lung metastasis, with parallel transcriptomic profiles indicating that the gene expression profile of the same tumor clone is altered by the tumor microenvironment. Furthermore, analysis of primary and recurrent human pancreatic neuroendocrine tumors reveals both persistent and newly emerging tumor subclones, exhibiting transcriptional changes in both the original and recurrence sites. These findings highlight Spatial-GT-seq as a valuable platform for studying genotype-phenotype-microenvironment associations, providing new insights into cancer evolution and heterogeneity.

  单细胞空间转录组多组学
• 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
• Inactivation of Irs1 in pericentral hepatocytes promotes lipid oxidation
  GSE349448Mus musculus4 个样本2026-10-30

  Hepatic metabolic zonation enables periportal (PP) and pericentral (PC) hepatocytes to perform distinct functions in glucose and lipid metabolism. Insulin signaling is also spatially organized across the liver lobule, but the transcriptional role of insulin signaling in PC hepatocytes remains incompletely understood. To define the gene-expression programs regulated by insulin signaling in PC hepatocytes, we generated mice with inducible PC-specific deletion of insulin receptor substrate 1 (Irs1) using Cyp1a2CreER (Irs1-Cyp1a2 mice). RNA sequencing was performed to compare liver gene-expression profiles between Irs1-Cyp1a2 mice and littermate controls. This dataset provides a transcriptomic resource for identifying pathways regulated by PC IRS1 signaling and for understanding how spatial insulin signaling contributes to hepatic glucose and lipid metabolism.

  空间转录组
• HOXA9 reprograms 3D genome architecture to regulate oncogenic transcription in acute myeloid leukemia [CUT&RUN]
  GSE301083Homo sapiens31 个样本2026-10-30

  The hierarchical three-dimensional (3D) organization of chromatin underpins the spatial and temporal control of gene expression during development. This principle is exemplified by the Hox gene clusters, where dynamic topological architecture governs precise transcriptional activation. While disruption of chromatin organization at Hox genes is increasingly recognized in various human malignancies, the extent to which Hox genes themselves contribute to shaping 3D genome architecture remains poorly understood. In particular, it is unknown whether oncogenic overexpression of HOXA9—a highly conserved transcription factor and common downstream effector of diverse genetic alterations in acute myeloid leukemia (AML)—can actively reprogram chromatin topology. Here, we uncover a pivotal role for HOXA9 as a master regulator of 3D chromatin architecture in human AML. We demonstrate that HOXA9 orchestrates a leukemia-specific reconfiguration of chromatin topology. HOXA9 promotes the formation of leukemia specific topologically associating domains (TADs) and establishes long-range enhancer–promoter interactions essential for maintaining the leukemic transcriptional program. Perturbation of HOXA9 leads to widespread architectural collapse, marked by the dissolution of chromatin loops, disrupted enhancer communication, and silencing of critical leukemogenic genes. Furthermore, HOXA9-mediated chromatin looping occurs independently of CTCF. Instead, HOXA9 functions through the cohesin complex to facilitate higher-order genome organization, thereby functioning as a non-canonical architectural factor. Among its targets, we identify NHLRC2 as a HOXA9-associated loop gene essential for leukemic cell survival and proliferation. Collectively, these findings uncover a previously unappreciated architectural function of HOXA9 in modulating 3D genome organization and sustaining oncogenic gene expression in AML. More broadly, they suggest a mechanistic paradigm in which HOX transcription factors actively reprogram nuclear architecture to enforce lineage-specific or malignant gene expression programs.

  空间转录组扰动筛选
• Epigenomic analysis of the myometrium during late implantation revealed regulatory elements in genes related to the cellular zinc homeostasis pathway in pigs (ChIP-Seq)
  GSE246433Sus scrofa12 个样本2026-10-30

  The myometrium, composed of the inner circular muscle (CM) and outer longitudinal muscle (LM), is crucial in establishing and maintaining early pregnancy. However, the molecular mechanisms involved are not well understood. In this study, we identified the transcriptomic features of the CM and LM collected from the mesometrial (M) and anti-mesometrial (AM) sides of the pig uterus on day 18 of pregnancy during the placentation initiation phase. Some genes in the cellular zinc ion level regulatory pathways (MT-1A, MT-1D, MT-2B, SLC30A2, and SLC39A2) were spatially and highly enriched in uterine CM at the mesometrial side. In addition, the histone modification profiles of H3K27ac and H3K4me3 in uterine CM and LM collected from the mesometrial side were characterized. Genomic regions associated with the expression of genes regulating the cellular zinc ion level were detected. Moreover, six highly linked variants in the H3K27ac-enriched region of the pig SLC30A2 gene were identified and found to be significantly associated with the total number born at the second parity (P < 0.05). In conclusion, the genes in the pathways of cellular zinc homeostasis and their regulatory elements identified have implications for pig reproduction trait improvement and warrant further investigations.

  空间转录组
• Epigenomic analysis of the myometrium during late implantation revealed regulatory elements in genes related to the cellular zinc homeostasis pathway in pigs (RNA-Seq)
  GSE246432Sus scrofa12 个样本2026-10-30

  The myometrium, composed of the inner circular muscle (CM) and outer longitudinal muscle (LM), is crucial in establishing and maintaining early pregnancy. However, the molecular mechanisms involved are not well understood. In this study, we identified the transcriptomic features of the CM and LM collected from the mesometrial (M) and anti-mesometrial (AM) sides of the pig uterus on day 18 of pregnancy during the placentation initiation phase. Some genes in the cellular zinc ion level regulatory pathways (MT-1A, MT-1D, MT-2B, SLC30A2, and SLC39A2) were spatially and highly enriched in uterine CM at the mesometrial side. In addition, the histone modification profiles of H3K27ac and H3K4me3 in uterine CM and LM collected from the mesometrial side were characterized. Genomic regions associated with the expression of genes regulating the cellular zinc ion level were detected. Moreover, six highly linked variants in the H3K27ac-enriched region of the pig SLC30A2 gene were identified and found to be significantly associated with the total number born at the second parity (P < 0.05). In conclusion, the genes in the pathways of cellular zinc homeostasis and their regulatory elements identified have implications for pig reproduction trait improvement and warrant further investigations.

  空间转录组
• Spatially resolved heterogeneity of lymphatic vasculature in the adult lung
  GSE325297Mus musculus2 个样本2026-10-29

  Background. Lung lymphatic drainage of interstitial fluid is essential for preventing pulmonary edema, a condition characterized by the accumulation of extravascular fluid that impedes respiratory gas exchange and can be fatal. Beyond fluid regulation, lung lymphatics also serve as conduits for immune cell trafficking, supporting both surveillance and mounting of host immune responses during lung infection. Despite their essential roles, the cellular and functional heterogeneity of lung lymphatic endothelial cells (LECs) remains poorly defined. Methods. Leveraging single nucleus sequencing technology, we investigated LEC heterogeneity in the homeostatic adult mouse lung. Results. We identified Stabilin-2 (Stab2), a Class H scavenger receptor, as a unique marker of a distinct subset of LECs in lymphatic vessels adjacent to pulmonary veins and in alveolar regions. A separate distinct subset of LECs is defined by expression of Polycystic Kidney and Hepatic Disease 1-Like-1 (Pkhd1l1), a component of stereocilia, and these lymphatic vessels are localized to the bronchovascular bundle. Conclusions. Our findings suggest that lung LECs are not a uniform population but instead compromise molecularly distinct and spatially organized lymphatic vessels, possibly with specialized functions. These results lay the groundwork for further studies geared towards understanding the roles of cellular origin in lung LEC heterogeneity, whether lymphatics in other organs have analogous spatial organization, and whether these disparate cells and vessels have functional differences in fluid homeostasis and immune regulation during pulmonary disease pathogenesis.

  单细胞空间转录组
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain [scRNA-seq]
  GSE314217Mus musculus491 个样本2026-10-29

  DNA methylation, particularly CpG methylation, plays a pivotal role in brain development, function, and aging. While recent single-cell brain methylome atlases have been mapped, they cannot distinguish between 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) due to their reliance on bisulfite conversion. This limitation is particularly problematic in the brain, where postmitotic neurons accumulate abundant 5hmCG, which may exert functions opposite to 5mCG. Consequently, how CpG modifications regulate neuronal gene expression remains incompletely understood. To address this, we present Joint-Cabernet, a bisulfite-free single-cell platform enabling simultaneous profiling of 5hmC, 5mC, and transcriptomes. Applying Joint-Cabernet to nuclei from adult mouse brains, we resolved cell-type-specific DNA hydroxymethylation landscapes, revealing elevated 5hmCG and 5hmCH levels in transcriptionally active genes and regulatory elements across diverse brain cell types and spatial gradients in cortical layers. This single-cell multi-omic atlas (DNA methylation, hydroxymethylation, and transcriptome) of the mouse brain provides a framework for studying methylation-driven regulation in the brain organization and neurodegenerative diseases.

  单细胞空间转录组细胞图谱多组学
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain [5mC]
  GSE314211Mus musculus479 个样本2026-10-29

  DNA methylation, particularly CpG methylation, plays a pivotal role in brain development, function, and aging. While recent single-cell brain methylome atlases have been mapped, they cannot distinguish between 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) due to their reliance on bisulfite conversion. This limitation is particularly problematic in the brain, where postmitotic neurons accumulate abundant 5hmCG, which may exert functions opposite to 5mCG. Consequently, how CpG modifications regulate neuronal gene expression remains incompletely understood. To address this, we present Joint-Cabernet, a bisulfite-free single-cell platform enabling simultaneous profiling of 5hmC, 5mC, and transcriptomes. Applying Joint-Cabernet to nuclei from adult mouse brains, we resolved cell-type-specific DNA hydroxymethylation landscapes, revealing elevated 5hmCG and 5hmCH levels in transcriptionally active genes and regulatory elements across diverse brain cell types and spatial gradients in cortical layers. This single-cell multi-omic atlas (DNA methylation, hydroxymethylation, and transcriptome) of the mouse brain provides a framework for studying methylation-driven regulation in the brain organization and neurodegenerative diseases.

  单细胞空间转录组细胞图谱多组学
• Single-cell Characterization of DNA Hydroxymethylation of the Mouse Brain [5hmC]
  GSE314195Mus musculus479 个样本2026-10-29

  DNA methylation, particularly CpG methylation, plays a pivotal role in brain development, function, and aging. While recent single-cell brain methylome atlases have been mapped, they cannot distinguish between 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) due to their reliance on bisulfite conversion. This limitation is particularly problematic in the brain, where postmitotic neurons accumulate abundant 5hmCG, which may exert functions opposite to 5mCG. Consequently, how CpG modifications regulate neuronal gene expression remains incompletely understood. To address this, we present Joint-Cabernet, a bisulfite-free single-cell platform enabling simultaneous profiling of 5hmC, 5mC, and transcriptomes. Applying Joint-Cabernet to nuclei from adult mouse brains, we resolved cell-type-specific DNA hydroxymethylation landscapes, revealing elevated 5hmCG and 5hmCH levels in transcriptionally active genes and regulatory elements across diverse brain cell types and spatial gradients in cortical layers. This single-cell multi-omic atlas (DNA methylation, hydroxymethylation, and transcriptome) of the mouse brain provides a framework for studying methylation-driven regulation in the brain organization and neurodegenerative diseases.

  单细胞空间转录组细胞图谱多组学
• Med1 Deletion Reprograms Dental Epithelium into Primitive Hair-Forming Epidermal Architecture via Trp63 Driven Epigenetic Alterations
  GSE316847Mus musculus1 个样本2026-10-28

  Ectodermal fate decisions between tooth enamel and skin hair are governed by transcription factors, epigenetic mechanisms, and tissue architecture. Deletion of the Mediator subunit Med1, which links enhancer activity to transcriptional output, induces a striking lineage conversion characterized by ectopic hair formation in mouse incisors. Here, we define the cellular, transcriptional, and epigenetic mechanisms underlying this process. Single-cell and spatial transcriptomic analyses reveal extensive remodeling of the incisor epithelium following Med1 deletion, whereby dental pre-ameloblasts and SI cells convert into hair germ–like populations resembling ancestral hair-initiating cells while retaining dental identity. Epidermal fate is driven by the master regulator Trp63, enabling hair formation without follicles distinguishing this process from canonical skin hair regeneration. Mechanistically, epigenetic changes occur in which TRP63 co-localized with alternative MED12-containing enhancers to activate itself and downstream epidermal genes. Together, these findings suggest that Med1 loss promotes hair formation through unique reprogramming to an evolutionarily primitive epidermal state rather than direct trans-differentiation to skin epithelium, providing new insights in ectodermal plasticity.

  单细胞空间转录组
• Med1 Deletion Reprograms Dental Epithelium into Primitive Hair-Forming Epidermal Architecture via Trp63 Driven Epigenetic Mechanisms
  GSE316208Mus musculus12 个样本2026-10-28

  Ectodermal fate decisions between tooth enamel and skin hair are governed by transcription factors, epigenetic mechanisms, and tissue architecture. Deletion of the Mediator subunit Med1, which links enhancer activity to transcriptional output, induces a striking lineage conversion characterized by ectopic hair formation in mouse incisors. Here, we define the cellular, transcriptional, and epigenetic mechanisms underlying this process. Single-cell and spatial transcriptomic analyses reveal extensive remodeling of the incisor epithelium following Med1 deletion, whereby dental pre-ameloblasts and SI cells convert into hair germ–like populations resembling ancestral hair-initiating cells while retaining dental identity. Epidermal fate is driven by the master regulator Trp63, enabling hair formation without follicles distinguishing this process from canonical skin hair regeneration. Mechanistically, epigenetic changes occur in which TRP63 co-localized with alternative MED12-containing enhancers to activate itself and downstream epidermal genes. Together, these findings suggest that Med1 loss promotes hair formation through unique reprogramming to an evolutionarily primitive epidermal state rather than direct trans-differentiation to skin epithelium, providing new insights in ectodermal plasticity.

  单细胞空间转录组
• Spatial transcriptomic profiling of human left ventricular tissue in ischaemic heart disease and dilated cardiomyopathy
  GSE351778Homo sapiens2 个样本2026-10-27

  Spatially resolved single-cell gene expression profiling was performed on fresh-frozen human left ventricular tissue from one ischaemic heart disease (IHD) and one dilated cardiomyopathy (DCM) specimen. The Xenium Human Multi-Tissue and Cancer Gene Expression panel supplemented with 100 custom probes was used to characterise cardiomyocytes and cardiac fibroblasts and investigate spatial relationships between fibroblast subpopulations and cardiomyocyte.

  单细胞空间转录组
• Genomic and Immune Profiling Characterizes Immune Heterogeneity and a TIGIT-Associated Subtype in Intrahepatic Cholangiocarcinoma
  GSE350183Homo sapiens164 个样本2026-10-27

  Background and Aims: Intrahepatic cholangiocarcinoma (iCCA) is characterised by marked molecular and microenvironmental heterogeneity and moderate response to immunotherapy. We aimed to define the genomic and spatial determinants of immune checkpoint activity in iCCA and their association with clinical outcome. Approach and Results: We performed integrated transcriptomic, DNA panel sequencing, and multiplex immunohistochemistry analyses in a cohort of 144 patients with iCCA. Tumors were classified according to STIM-defined microenvironmental subtypes. Spatially resolved immune profiling was conducted across tumor core, stroma, invasive margin, and adjacent liver. Immune checkpoint expression, cellular proximity, and clinical outcome were analysed using Cox regression and Kaplan-Meier methods. TIGIThigh tumors were further characterised by differential gene expression and pathway enrichment analyses. STIM classification stratified tumors into inflamed (47%) and non-inflamed (53%) subtypes with distinct survival outcomes and genomic profiles. Recurrent alterations in CDKN2A/B, TP53, MTAP, and BAP1 showed subtype-specific enrichment and prognostic relevance. Spatial immune profiling revealed compartment-specific distributions of T cells and immune checkpoints, with predominance of TIGIT and PD-1 expression in stromal and marginal regions. Most tumor-infiltrating T cells lacked inhibitory receptor expression, while co-expression of multiple checkpoints was uncommon. TIGIThigh tumors displayed coordinated activation of immune effector, antigen presentation, and interferon signalling pathways, alongside enrichment of distinct genomic alterations, defining an immune-activated molecular subtype. Conclusions: Integrated genomic and spatial immune profiling reveals pronounced context-dependent heterogeneity of immune checkpoint regulation in iCCA. TIGIT delineates an immune-activated subtype with distinct molecular features, providing a potential biomarker framework for patient stratification and rational immunotherapeutic targeting.

  空间转录组
• Microglial lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348401Mus musculus8 个样本2026-10-27

  Glioblastoma (GBM) is characterized by diffuse infiltration into the surrounding brain, limiting complete surgical resection, the strongest determinant of patient survival. The mechanisms driving this invasive growth remain incompletely understood. Here, we identify a lipid-mediated paracrine signaling axis through which tumor-associated microglia/macrophages promote glioma invasion. Integrating single-cell transcriptomics, spatial lipidomics, and functional perturbation across mouse models and human GBM samples, we show that invading tumor cells engage and reprogram myeloid cells via CSF1R–PI3K signaling. This induces lipid metabolic reprogramming and secretion of bioactive lipids, including lysophosphatidylcholines (LPCs) and lysophosphatidic acids (LPAs), which promote GBM invasion through distinct downstream pathways. Disruption of this myeloid–GBM axis, reduces lipid secretion and suppresses invasion. Targeting downstream LPA–LPAR or YAP/TAZ signaling further constrains invasion in a context-dependent manner. Together, these findings define a lipid-driven circuit linking the tumor microenvironment to glioma invasion and identify strategies to reduce infiltration and improve surgical resection.

  单细胞空间转录组扰动筛选
• Macrophage lipid signaling drives glioblastoma invasion and represents a therapeutic vulnerability
  GSE348147Mus musculus16 个样本2026-10-27

  Glioblastoma (GBM) is characterized by diffuse infiltration into the surrounding brain, limiting complete surgical resection, the strongest determinant of patient survival. The mechanisms driving this invasive growth remain incompletely understood. Here, we identify a lipid-mediated paracrine signaling axis through which tumor-associated microglia/macrophages promote glioma invasion. Integrating single-cell transcriptomics, spatial lipidomics, and functional perturbation across mouse models and human GBM samples, we show that invading tumor cells engage and reprogram myeloid cells via CSF1R–PI3K signaling. This induces lipid metabolic reprogramming and secretion of bioactive lipids, including lysophosphatidylcholines (LPCs) and lysophosphatidic acids (LPAs), which promote GBM invasion through distinct downstream pathways. Disruption of this myeloid–GBM axis, reduces lipid secretion and suppresses invasion. Targeting downstream LPA–LPAR or YAP/TAZ signaling further constrains invasion in a context-dependent manner. Together, these findings define a lipid-driven circuit linking the tumor microenvironment to glioma invasion and identify strategies to reduce infiltration and improve surgical resection.

  单细胞空间转录组扰动筛选
• 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
• Single Cell multi-omics identifies VEGFA-mediated angiogenesis results in relapse in Sonic Hedgehog Medulloblastoma [Visium]
  GSE287107Homo sapiens6 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
• Molecular mapping of developing synovial fibroblasts in the TMJ reveals the crucial role of mechanical force in cavitation
  GSE351686Homo sapiens3 个样本2026-10-26

  The temporomandibular joint is formed from neural crest-derived mesenchyme with delayed development, distinct from other mesodermal derived majority synovial joints. Here, we perfomed spatial transcriptomics on human embryo samples at the initiation and cavitation stage from 9th , 10th and 11th post-conception weeks (PCW) to profile cellualr identity, singalling activity, extracellular matrix dynamics and ligand-receptor interactions during TMJ development. Our analysis has indicated the significant roles of synoival fibroblasts during the cavitation stage in the developing TMJ.

  空间转录组