Nonbone Marrow CD34+ Cells Are Crucial for Endothelial Repair of Injured Artery. Issue 8 (3rd September 2021)

• Record Type: Journal Article
• Authors: Jiang, Liujun; Chen, Ting; Sun, Shasha; Wang, Ruilin; Deng, Jiacheng; Lyu, Lingxia; Wu, Hong; Yang, Mei; Pu, Xiangyuan; Du, Luping; Chen, Qishan; Hu, Yanhua; Hu, Xiaosheng; Zhou, Yijiang; Xu, Qingbo; Zhang, Li
• Is Part Of: Circulation research. Volume 129:Issue 8(2021)
• Page Start: e146
• Page End: e165
• Publication Date: 2021-09-03
• Subjects: CD34 antigens -- endothelial cells -- fluorescent antibody technique -- microRNAs -- RNA sequence analysis -- smad proteins -- vascular system injuries; Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.121.319494
• Languages: English
• ISSNs: 0009-7330

Abstract

Abstract : Supplemental Digital Content is available in the text. Abstract : 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 microRNA-21-Smad7-pSmad2/3 pathway regulated endothelial gene expression and function during differentiation. Conclusions: Our study provides a transcriptional and cellular landscape of vessels after endothelial denudation. Our findings suggest heterogeneous CD34 + cells serve as a contributor not only to endothelial regeneration but also an inflammatory response that may provide therapeutic insights into vascular diseases.