Single-cell gene profiling and lineage tracing analyses revealed novel mechanisms of endothelial repair by progenitors

Jiacheng Deng, Zhichao Ni, Wenduo Gu, Qishan Chen, Witold Norbert Nowak, Ting Chen, Shirin Issa Bhaloo, Zhongyi Zhang, Yanhua Hu, Bin Zhou, Li Zhang*, Qingbo Xu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Stem/progenitor cells (SPCs) have been implicated to participate in vascular repair. However, the exact role of SPCs in endothelial repair of large vessels still remains controversial. This study aimed to delineate the cellular heterogeneity and possible functional role of endogenous vascular SPCs in large vessels. Using single-cell RNA-sequencing (scRNA-seq) and genetic lineage tracing mouse models, we uncovered the cellular heterogeneity of SPCs, i.e., c-Kit+ cells in the mouse aorta, and found that endogenous c-Kit+ cells acquire endothelial cell fate in the aorta under both physiological and pathological conditions. While c-Kit+ cells contribute to aortic endothelial turnover in the atheroprone regions during homeostasis, recipient c-Kit+ cells of nonbone marrow source replace both luminal and microvessel endothelial cells in transplant arteriosclerosis. Single-cell pseudotime analysis of scRNA-seq data and in vitro cell experiments suggest that vascular SPCs display endothelial differentiation potential and undergo metabolic reprogramming during cell differentiation, in which AKT/mTOR-dependent glycolysis is critical for endothelial gene expression. These findings demonstrate a critical role for c-Kit lineage cells in aortic endothelial turnover and replacement, and may provide insights into therapeutic strategies for vascular diseases.

Original languageEnglish
Pages (from-to)5299-5320
Number of pages22
JournalCellular and Molecular Life Sciences
Issue number24
Publication statusPublished - Dec 2020


  • Endothelial repair
  • Lineage tracing
  • Metabolism
  • Single-cell RNA-sequencing
  • Stem cells


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