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Resident vascular Sca1+ progenitors differentiate into endothelial cells in vascular remodeling via miR-145-5p/ERG signaling pathway

Authors :
Zhangquan Ying
Lingxia Lyu
Xiaodong Xu
Zuoshi Wen
Jianing Xue
Mengjia Chen
Zhoubin Li
Liujun Jiang
Ting Chen
Source :
iScience, Vol 27, Iss 6, Pp 110080- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: Endothelial cell (EC) damage or dysfunction serves as the initial event in the pathogenesis of various cardiovascular diseases. Progenitor cells have been postulated to be able to differentiate into ECs, facilitate endothelial regeneration, and alleviate vascular pathological remodeling. However, the precise cellular origins and underlying mechanisms remain elusive. Through single-cell RNA sequencing (scRNA-seq), we identified an increasing population of progenitors expressing stem cell antigen 1 (Sca1) during vascular remodeling in mice. Using both mouse femoral artery injury and vein graft models, we determined that Sca1+ cells differentiate into ECs, restored endothelium in arterial and venous remodeling processes. Notably, we have observed that the differentiation of Sca1+ cells into ECs is negatively regulated by the microRNA-145-5p (miR-145-5p)-Erythroblast transformation-specific-related gene (ERG) pathway. Inhibiting miR-145-5p promoted Sca1+ cell differentiation and reduced neointimal formation after vascular injury. Finally, a similar downregulation of miR-145-5p in human arteriovenous fistula was observed comparing to healthy veins.

Details

Language :
English
ISSN :
25890042
Volume :
27
Issue :
6
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.6a722633ed7b499b9301714729fbad7b
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2024.110080