Hierarchical organization and early hematopoietic specification of the developing HSC lineage in the AGM region

Abstract

The aorta-gonad-mesonephros region plays an important role in hematopoietic stem cell (HSC) development during mouse embryogenesis. The vascular endothelial cadherin+ CD45+ (VE-cad+CD45+) population contains the major type of immature pre-HSCs capable of developing into long-term repopulating definitive HSCs. In this study, we developed a new coaggregation culture system, which supports maturation of a novel population of CD45-negative (VE-cad+CD450-CD41+) pre-HSCs into definitive HSCs. The appearance of these pre-HSCs precedes development of the VE-cad+CD45+ pre-HSCs (termed here type I and type II pre-HSCs, respectively), thus establishing a hierarchical directionality in the developing HS..