ArticleExperimental & molecular medicine2023
Single-cell sequencing reveals that endothelial cells, EndMT cells and mural cells contribute to the pathogenesis of cavernous malformations.
Article in Experimental & molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Comprehensive Integration of Multiple Single-Cell Transcriptomic Data Sets Defines Distinct Cell Populations and Their Phenotypic Changes in Murine Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2024Pooled it
- EndMT in vascular cognitive impairment and dementia: mechanisms, evidence gaps, and therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
- Single-cell and spatial transcriptomics identify immune-stromal interactions in cardiac allograft vasculopathy.Nature cardiovascular research · 2026Article
- Defining the vascular niche of human adipose tissue across metabolic states.Nature metabolism · 2026Article
- Scar-associated endothelial-stellate cellular crosstalk drives fibrosis resolution in MASH.Cell reports · 2026Article
- Endothelial-Mesenchymal transition in cerebrovascular diseases: molecular mechanisms and promising pharmacological strategies.Molecular biology reports · 2026Review
- Single Cell and Spatial Transcriptomics Identify Novel Immune-Stromal Interactions in Cardiac Allograft Vasculopathy.Research square · 2025Article
- Endothelial-to-mesenchymal transition in the central nervous system: A potential therapeutic target to combat age-related vascular fragility.The Journal of pharmacology and experimental therapeutics · 2025Review
- Defining the vascular niche of human adipose tissue across metabolic states.bioRxiv : the preprint server for biology · 2025Article
- Single-Cell Transcriptome Profiling Reveals Dynamic Cell Populations and Immune Infiltration in Moyamoya Disease.Journal of the American Heart Association · 2025Article
- High-throughput differentiation of human blood vessel organoids reveals overlapping and distinct functions of the cerebral cavernous malformation proteins.Angiogenesis · 2025Article
- Single-Cell Analysis in Cerebrovascular Research: Primed for Breakthroughs and Clinical Impact.Stroke · 2025Review
- Single-Cell Transcriptomic Reveals the Involvement of Cell-Cell Junctions in the Early Development of Hypertrophic Cardiomyopathy.Journal of cellular and molecular medicine · 2025Article
- Broadening horizons: molecular mechanisms and disease implications of endothelial-to-mesenchymal transition.Cell communication and signaling : CCS · 2025Review
- Qimai Feiluoping Decoction Inhibits EndMT to Alleviate Pulmonary Fibrosis by Reducing PI3K/AKT/mTOR Pathway-Mediated the Restoration of Autophagy.Journal of inflammation research · 2025Article
- Single-cell RNA sequencing reveals endothelial cell heterogeneity and Sox18-mediated EndMT in abdominal aortic aneurysm.Theranostics · 2025Article
- Article
- Pharmacological blocking of neutrophil extracellular traps attenuates immunothrombosis and neuroinflammation in cerebral cavernous malformation.Nature cardiovascular research · 2024Article
- Liver ACSM3 deficiency mediates metabolic syndrome via a lauric acid-HNF4α-p38 MAPK axis.The EMBO journal · 2024Article
- Transcriptomic signatures of individual cell types in cerebral cavernous malformation.Cell communication and signaling : CCS · 2024Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cavernous malformations (CMs) invading the central nervous system occur in ~0.16-0.4% of the general population, often resulting in hemorrhages and focal neurological deficits. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of CMs in humans. Herein, we performed single-cell RNA sequencing (scRNA-seq) analysis on unselected viable cells from twelve human CM samples and three control samples. A total of 112,670 high-quality cells were clustered into 11 major cell types, which shared a number of common features in CMs harboring different genetic mutations. A new EC subpopulation marked with PLVAP was uniquely identified in lesions. The cellular ligand‒receptor network revealed that the PLVAP-positive EC subcluster was the strongest contributor to the ANGPT and VEGF signaling pathways in all cell types. The PI3K/AKT/mTOR pathway was strongly activated in the PLVAP-positive subcluster even in non-PIK3CA mutation carriers. Moreover, endothelial-to-mesenchymal transition (EndMT) cells were identified for the first time in CMs at the single-cell level, which was accompanied by strong immune activation. The transcription factor SPI1 was predicted to be a novel key driver of EndMT, which was confirmed by in vitro and in vivo studies. A specific fibroblast-like phenotype was more prevalent in lesion smooth muscle cells, hinting at the role of vessel reconstructions and repairs in CMs, and we also confirmed that TWIST1 could induce SMC phenotypic switching in vitro and in vivo. Our results provide novel insights into the pathomechanism decryption and further precise therapy of CMs.
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