Lin, YangBanno, KimihikoGil, Chang-HyunMyslinski, JeredHato, TakashiShelley, William C.Gao, HongyuXuei, XiaolingBasile, David P.Yoshimoto, MomokoPrasain, NutanTarnawsky, Stefan P.Adams, Ralf H.Naruse, KatsuhikoYoshida, JunkoMurphy, Michael P.Horie, KyojiYoder, Mervin C.2023-12-212023-12-212023-03-08Lin Y, Banno K, Gil CH, et al. Origin, prospective identification, and function of circulating endothelial colony-forming cells in mice and humans. JCI Insight. 2023;8(5):e164781. Published 2023 Mar 8. doi:10.1172/jci.insight.164781https://hdl.handle.net/1805/37480Most circulating endothelial cells are apoptotic, but rare circulating endothelial colony-forming cells (C-ECFCs), also known as blood outgrowth endothelial cells, with proliferative and vasculogenic activity can be cultured; however, the origin and naive function of these C-ECFCs remains obscure. Herein, detailed lineage tracing revealed murine C-ECFCs emerged in the early postnatal period, displayed high vasculogenic potential with enriched frequency of clonal proliferative cells compared with tissue-resident ECFCs, and were not committed to or derived from the BM hematopoietic system but from tissue-resident ECFCs. In humans, C-ECFCs were present in the CD34bright cord blood mononuclear subset, possessed proliferative potential and in vivo vasculogenic function in a naive or cultured state, and displayed a single cell transcriptome sharing some umbilical venous endothelial cell features, such as a higher protein C receptor and extracellular matrix gene expression. This study provides an advance for the field by identifying the origin, naive function, and antigens to prospectively isolate C-ECFCs for translational studies.en-USAttribution 4.0 InternationalVascular biologyEndothelial cellsExtracellular matrixArticle