Single-cell sequencing reveals the existence of fetal vascular endothelial stem cell-like cells in mouse liver

Abstract

Abstract Background 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. Methods We applied single-cell RNA sequencing of endothelial cells (ECs) from embryonic day (E) 14, E18, postnatal day (P) 7, P14, and week (W) 8 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+ ECs in the perinatal period. Results 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 toward adult VESC-like cells expressing CD157 and CD200 1 week after birth. Conclusion Our study provides a comprehensive atlas of liver EC development and documents VESC-like cell lineage commitment at single-cell resolution.

Keywords

• Single-cell transcriptomic sequencing
• Endothelial stem cells
• Heterogeneity
• Mouse liver
• Trajectory analysis
• RNA velocity