Most 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.


Yang Lin, Kimihiko Banno, Chang-Hyun Gil, Jered Myslinski, Takashi Hato, William C. Shelley, Hongyu Gao, Xiaoling Xuei, Yunlong Liu, David P. Basile, Momoko Yoshimoto, Nutan Prasain, Stefan P. Tarnawsky, Ralf H. Adams, Katsuhiko Naruse, Junko Yoshida, Michael P. Murphy, Kyoji Horie, Mervin C. Yoder


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