Nonbone Marrow CD34 + Cells Are Crucial for Endothelial Repair of Injured Artery
| Autor: | Xiaosheng Hu, Qingbo Xu, Ruilin Wang, Lingxia Lyu, Li Zhang, Hong Wu, Yijiang Zhou, Liujun Jiang, Yanhua Hu, Jiacheng Deng, Mei Yang, Qishan Chen, Shasha Sun, Luping Du, Ting Chen, Xiangyuan Pu |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Circulation Research. 129 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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