Most circulating endothelial cells are apoptotic, but rare circulating endothelial colony forming cells (C-ECFCs, also known as blood outgrowth endothelial cells (BOECs)) with proliferative and vasculogenic activity can be cultured; the origin and naïve function of these C-ECFCs remains obscure. Herein, detailed lineage tracing reveals murine C-ECFCs emerge in the early postnatal period, display high vasculogenic potential, with enriched frequency of clonal proliferative cells compared to tissue-resident ECFCs, and are not committed to or derived from the bone marrow hematopoietic system but from tissue-resident ECFCs. In human subjects, C-ECFCs are present in the CD34bright cord blood mononuclear subset, possess proliferative potential and in vivo vasculogenic function in a naïve or cultured state, and display a single cell transcriptome sharing some umbilical venous endothelial cell features like, higher Protein C Receptor and extracellular matrix gene expression. This study provides an advance for the field by identifying the origin, naïve function, and antigens to prospectively isolate C-ECFCs for translational studies.


Yang Lin, Kimihiko Banno, Chang-Hyun Gil, Jered Myslinski, Takashi Hato, W. Christopher Shelley, Hongyu Gao, Xiaoling Xuei, Yunlong Liu, David 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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