Nonbone Marrow CD34 + Cells Are Crucial for Endothelial Repair of Injured Artery

作者：Liujun Jiang, Ting Chen, Shasha Sun, Ruilin Wang, Jiacheng Deng, Lingxia Lyu, Hong Wu, Mei Yang, Xiangyuan Pu, Luping Du, Qishan Chen, Yanhua Hu, Xiaosheng Hu, Yijiang Zhou, Qingbo Xu, Li Zhang · 发表于：Circulation Research · 年份：2021 · DOI：10.1161/circresaha.121.319494 · 被引用次数：74 · 研究领域：Angiogenesis and VEGF in Cancer、Peripheral Artery Disease Management、Cardiac and Coronary Surgery Techniques

Rationale: Endothelial cells play a critical role in multiple cardiovascular diseases. Circulating CD34 + cells are believed to be endothelial progenitors that have been used to treat cardiovascular diseases. However, the exact identity and the role of CD34 + cells in vascular regeneration remains unclear. Objective: We aimed to investigate the exact identity and the role of CD34 + cells in vascular regeneration. Methods and Results: Compared with healthy arteries, CD34 expression percentage was significantly increased in diseased femoral arteries from patients. Using a guidewire-induced endothelial denudation model, we reported the transcriptional profiling of over 30 000 cells by single-cell RNA sequencing analysis and provided a cell atlas of normal and lesioned arteries in mouse, in which a heterogeneous population of CD34 + cells was revealed. Combining the inducible lineage tracing Cd34 -CreER T2 ;R26-tdTomato mouse model and bone marrow transplantation experiments, we showed that nonbone marrow CD34 + mesenchymal cells acquired endothelial cell fate in the injured femoral artery rather than preexiting endothelial cells, while bone marrow-derived CD34 + cells differentiated into immune cells locally after vessel injury. Depletion of nonbone marrow CD34 + cells using diphtheria toxin-induced cell ablation models exacerbate neointimal lesions of the injured vessel. Furthermore, isolated vascular adventitia CD34 + cells displayed endothelial differentiation, in which micro...