Single-Cell Sequencing Reveals the Existence of Fetal Vascular Endothelial Stem Cell-Like Cells in the Liver

A resident vascular endothelial stem cell (VESC) population expressing CD157 and CD200 has been identified recently in the adult mouse. However, the origin of this population and how it develops has not been characterized, nor has it been determined whether VESC-like cells are present during the perinatal period. Here, we investigated the presence of perinatal VESC-like cells and their relationship with the adult VESC-like cell population. We applied single-cell RNA sequencing of endothelial cells (ECs) from embryonic stage liver and investigated transcriptomic changes during liver EC development. We performed flow cytometry, immunofluorescence, colony formation assays and transplantation assays to validate the presence of and to assess the function of CD157+ and CD200+ endothelial cells (ECs) in the perinatal period. We identified CD200-expressing VESC-like cells in the perinatal period. These cells formed colonies in vitro and had high proliferative ability. The RNA Velocity tool and transplantation assay results indicated that the projected fate of this population was towards adult VESC-like cells expressing CD157 and CD200 one week after birth. Our study provides a comprehensive atlas of liver EC development and documents VESC-like cell lineage commitment at single-cell resolution. Overall design: Single cell RNA sequencing of liver endothelial cells along from Embrionic Stage