VE-cadherin and ACE co-expression marks highly proliferative hematopoietic stem cells in human embryonic liver.

Despite advances to engineer transplantable hematopoietic stem and progenitor cells (HSPCs) for research and therapy, an in depth characterization of the developing human hematopoietic system is still lacking. The human embryonic liver is at the crossroad of several hematopoietic sites and harbors a complex hematopoietic hierarchy including the first, actively dividing HSPCs that will further seed the definitive hematopoietic organs. However few are known about the phenotypic and functional HSPC organization operating at these stages of development. Here, by using a combination of four endothelial and hematopoietic surface markers i.e. the endothelial-specific marker VE-cadherin, the pan-leukocyte antigen CD45, the hemato-endothelial marker CD34 and the Angiotensin-Converting Enzyme (ACE, CD143), we identified distinct HSCP subsets, among them, a population co-expressing the four markers that uniquely harbored an outstanding proliferation potential both ex vivo and in vivo. Moreover, we traced back this population to the yolk sac and AGM sites of hematopoietic emergence. Taken together, our data will help to identify human HSPC self-renewal and amplification mechanisms for future cell therapies.