Arterial Sca1 Vascular Stem Cells Generate De Novo Smooth Muscle for Artery Repair and Regeneration
Authors: Li Zhang
Huan Zhu
Lingjuan He
Fei Li
Jacob Fog Bentzon
Xiuzhen Huang
Yu Nie
Bin Zhou
Yan Li
Yong Ji
Haixiao Wang
Kuo Liu
Juan Tang
Hui Zhang
Ying Yu
Wenjuan Pu
Dong Gao
Huan Zhao
Xueying Tian
Journal: Cell stem cell (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Sca1; YAP; dual recombinase; genetic lineage; vascular stem cell
Affiliations: The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China., School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain; Deparment of Clinical Medicine, Aarhus University, Aarhus, Denmark., Department of Pharmacology and Tianjin Key Laboratory of Inflammatory Biology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China., Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing 211100, China; The Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211100, China., State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Key Laboratory of Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou 510632, China., The Department of Cardiology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: ., The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. Electronic address: ., The State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Key Laboratory of Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou 510632, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. Electronic address: .

Abstract:  Rapid regeneration of smooth muscle after vascular injury is essential for maintaining arterial function. The existence and putative roles of resident vascular stem cells (VSCs) in artery repair are controversial, and vessel regeneration is thought to be mediated by proliferative expansion of pre-existing smooth muscle cells (SMCs). Here, we performed cell fate mapping and single-cell RNA sequencing to identify Sca1+ VSCs in the adventitial layer of artery walls. After severe injury, Sca1+ VSCs migrate into the medial layer and generate de novo SMCs, which subsequently expand more efficiently compared with pre-existing smooth muscle. Genetic lineage tracing using dual recombinases distinguished a Sca1+PDGFRa+ VSC subpopulation that generates SMCs, and genetic ablation of Sca1+ VSCs or specific knockout of Yap1 in Sca1+ VSCs significantly impaired artery repair. These findings provide genetic evidence of a bona fide Sca1+ VSC population that produces SMCs and delineates their critical role in vessel repair. 

Retracted: No

PubPeer comments:
 Nice work, but it would be more instructive if authors discussed their results with the perspective of previous published results in the field: - Sca1+ cells contribute to cardiac turnover: Sca1-derived Cells Are a Source of Myocardial Renewal in the Murine Adult Heart. Stem Cell Reports . 2013 Oct 24;1(5):397-410. Genetic Lineage Tracing of Sca-1+ Cells Reveals Endothelial but Not Myogenic Contribution to the Murine Heart. Circulation. 2018;138:2931u20132939 Bmi1-Progenitor Cell Ablation Impairs the Angiogenic Response to Myocardial Infarction. Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2160-2173. doi: 10.1161 ATVBAHA.118.310778. - Cardiac vasculature is a niche-like structure for some Sca1+ cell populations: Age-related oxidative stress confines damage-responsive Bmi1+ cells to perivascular regions in the murine adult heart. Redox Biol. 2019 Apr;22:101156. ,