State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, CAS, Shanghai 200031, China.
Development. 2022 Jun 15;149(12). doi: 10.1242/dev.200419. Epub 2022 Jun 22.
Vascular establishment is one of the early events in embryogenesis. It is believed that vessel-initiating endothelial progenitors cluster to form the first primitive vessel. Understanding the molecular identity of these progenitors is crucial in order to elucidate lineage hierarchy. In this study, we identify protein C receptor (Procr) as an endothelial progenitor marker and investigate the role of Procr+ progenitors during embryonic vascular development. Using a ProcrmGFP-2A-lacZ reporter, we reveal a much earlier Procr expression (embryonic day 7.5) than previously acknowledged (embryonic day 13.5). Genetic fate-mapping experiments using ProcrCre and ProcrCreER demonstrate that Procr+ cells give rise to blood vessels throughout the entire embryo proper. Single-cell RNA-sequencing analyses place Procr+ cells at the start of endothelial commitment and maturation. Furthermore, targeted ablation of Procr+ cells results in failure of vessel formation and early embryonic lethality. Notably, genetic fate mapping and scRNA-seq pseudotime analysis support the view that Procr+ progenitors can give rise to hemogenic endothelium. In this study, we establish a Procr expression timeline and identify Procr+ vessel-initiating progenitors, and demonstrate their indispensable role in establishment of the vasculature during embryo development.
血管生成是胚胎发生过程中的早期事件之一。人们认为，起始内皮祖细胞聚集形成第一个原始血管。为了阐明谱系层次结构，了解这些祖细胞的分子特征至关重要。在这项研究中，我们确定了蛋白 C 受体（Procr）作为内皮祖细胞标志物，并研究了 Procr+祖细胞在胚胎血管发育过程中的作用。使用 ProcrmGFP-2A-lacZ 报告基因，我们揭示了比以前认识到的更早的 Procr 表达（胚胎第 7.5 天）。使用 ProcrCre 和 ProcrCreER 的遗传谱系追踪实验表明，Procr+细胞产生整个胚胎的血管。单细胞 RNA 测序分析将 Procr+细胞置于内皮细胞定型和成熟的起点。此外，Procr+细胞的靶向消融导致血管形成失败和早期胚胎致死。值得注意的是，遗传谱系追踪和 scRNA-seq 拟时分析支持 Procr+祖细胞可以产生造血内皮的观点。在这项研究中，我们建立了 Procr 表达时间轴，并确定了 Procr+血管起始祖细胞，并证明了它们在胚胎发育过程中血管建立中的不可或缺作用。
