Endothelial colony-forming cells (ECFCs) are the progenitor cells that can give rise to colonies of highly proliferative vascular endothelial cells (ECs) with clonal expansion and in vivo blood vessel-forming potential. The discovery of ECFCs could impact on multiple vascular diseases as a clinically accessible source of autologous ECs. However, the field of endothelial progenitor cells has been plagued with ambiguities and controversies. One of the major reasons for the conundrum is insufficient insights in the biological attributes of ECFCs (Cold Spring Harb Perspect Med (2022) 12: a041154). The authors focused on the identification of cell lineages of circulating ECFCs (C-ECFCs) in mouse and human. For the mouse study, they utilized mouse lines expressing fluorescent proteins in specific blood cell lineages. They grafted cultured or partially purified blood cells from these mouse lines into normal mice, and examined if the grafted cells became endothelial cells in the new hosts. The author concluded that C-ECFCs were from resident endothelial cells but not umbilical cords and compared the gene expression profile in the cord blood mono nuclear cells (CBMCs) to that in endothelial cells isolated from the vein of umbilical cord (HUVEC). They discovered that a subpopulation of CBMCs shared similar gene expression profiles to HUVEC Importantly, this CBMC subpopulation of CBMCs shared similar gene expression profiles to HUVEC utilized multiple robust approaches including unbiased experimental designs, and would be influential to solve the conundrum described above.
