SINGLE-CELL TRANSCRIPTOMICS REVEALS A CD31+CD105- SUBPOPULATION OF EARLY ENDOTHELIAL CELLS WITH ELEVATED HEMATOPOIETIC POTENTIAL FROM HPSCS

Accumulating evidence shows that endothelial cells are the origin of blood cells both in vitro and in vivo. However, the heterogeneous nature of endothelial cells and the mechanism regulating their derivation remain largely elusive. In this study, we found by using single-cell transcriptomics analysis that CD31+ endothelial cells are highly heterogeneous even at its emergence from human pluripotent stem cells (hPSCs). Among them, a CD31+CD105- subpopulation of cells are highly potent for hematopoietic differentiation. Interestingly, genetic deletion of CD105 promotes the hematopoietic differentiation of hPSCs. While inhibition of TGFβ signaling facilitates the generation of CD31+CD105- subpopulation of cells, overexpression ETS1 suppresses its derivation. Our findings indicate that CD105 can be used as a reliable surface marker to enrich hematopoietic potent endothelial cells. The discovery of the underlying mechanism should also benefit the derivation of functional blood cells from hPSCs for translational medicine.