Arterial Sca1+ Vascular Stem Cells Generate De Novo Smooth Muscle for Artery Repair and Regeneration.,Cell Stem Cell

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Arterial Sca1+ Vascular Stem Cells Generate De Novo Smooth Muscle for Artery Repair and Regeneration.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-12-27 , DOI: 10.1016/j.stem.2019.11.010
Juan Tang ₁ , Haixiao Wang ₁ , Xiuzhen Huang ₁ , Fei Li ₁ , Huan Zhu ₁ , Yan Li ₁ , Lingjuan He ₁ , Hui Zhang ₂ , Wenjuan Pu ₁ , Kuo Liu ₃ , Huan Zhao ₁ , Jacob Fog Bentzon ₄ , Ying Yu ₅ , Yong Ji ₆ , Yu Nie ₇ , Xueying Tian ₈ , Li Zhang ₉ , Dong Gao ₁₀ , Bin Zhou ₁₁

Affiliation

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.
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.
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.

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.

中文翻译：

动脉Sca1 +血管干细胞产生从头开始的平滑肌，用于动脉修复和再生。

血管损伤后平滑肌的快速再生对于维持动脉功能至关重要。驻留的血管干细胞（VSCs）在动脉修复中的存在和假定的作用是有争议的，血管再生被认为是由先前存在的平滑肌细胞（SMCs）的增殖性介导的。在这里，我们进行了细胞命运定位和单细胞RNA测序，以鉴定动脉壁外膜层中的Sca1 + VSC。严重受伤后，Sca1 + VSCs迁移到内侧层并产生新生SMC，与先前存在的平滑肌相比，SMC可以更有效地扩展。使用双重重组酶进行的遗传谱系追踪可区分产生SMC的Sca1 + PDGFRa + VSC亚群，Sca1 + VSC的遗传消融或Sca1 + VSC中Yap1的特异性敲除显着损害了动脉修复。这些发现提供了真正的Sca1 + VSC种群的遗传证据，该种群产生SMC，并描述了它们在血管修复中的关键作用。

更新日期：2019-12-27

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