Accession PRJCA003143
Title Single-cell RNA-seq reveals lineage-specific regulatory changes of fibroblasts and vascular endothelial cells in keloids
Relevance Medical
Data types Transcriptome or Gene expression
Organisms Homo sapiens
Description Keloids are a benign dermal fibrotic disorder with features similar to malignant tumors. keloids remain a therapeutic challenge and lack medical therapies, which is partially due to the incomplete understanding of the pathogenesis mechanism. We performed single-cell RNA-seq of 28,064 cells from keloid skin tissue and adjacent relatively normal tissue. Unbiased clustering revealed substantial cellular heterogeneity of keloid tissue, which included 21 clusters assigned to 11 cell lineages. We observed significant expansion of fibroblast and vascular endothelial cell subpopulations in keloids, reflecting their strong association with keloid pathogenesis. Comparative analyses were performed to identify the dysregulated pathways, regulators and ligand-receptor interactions in keloid fibroblasts and vascular endothelial cells. Our results highlight the roles of transforming growth factor beta and Eph-ephrin signaling pathways in both the aberrant fibrogenesis and angiogenesis of keloids. Critical regulators probably involved in the fibrogenesis of keloid fibroblasts, such as TWIST1, FOXO3 and SMAD3, were identified. TWIST1 inhibitor harmine could significantly suppress the fibrogenesis of keloid fibroblasts. In addition, tumor-related pathways were activated in keloid fibroblasts and vascular endothelial cells, which may be responsible for the malignant features of keloids. Our study provides novel insights into the pathogenesis of keloids and potential targets for medical therapies
Sample scope Single cell
Release date 2020-07-29
Publication
PubMed ID Article title Journal name DOI Year
34242659 Single-Cell RNA-Sequencing Reveals Lineage-Specific Regulatory Changes of Fibroblasts and Vascular Endothelial Cells in Keloids Journal of Investigative Dermatology 10.1016/j.jid.2021.06.010 2022
Grants
Agency program Grant ID Grant title
National Natural Science Foundation of China (NSFC) 81870229
Submitter Zhou    Zhou  (zhouzhoufuwai@126.com)
Organization Fuwai Hospital, Chinese Academy of Medical Sciences
Submission date 2020-07-29

Project Data

Resource name Description
BioSample (8)  show -