Developmental Origins of the Heterogeneous Hematopoiesis

Hematopoietic stem and progenitor cells (HSPCs) are initially generated during embryogenesis, laying the foundation for the hematopoietic system. These embryonic HSPCs exhibit functional heterogeneity, which is essential for their diverse roles in both fetal and adult hematopoiesis. Growing evidence suggests that this heterogeneity arises from hemogenic endothelium (HE), a specialized subset of endothelial precursors with hematopoietic potential. Additionally, studies show that hematopoietic stem cells (HSCs) and multipotent hematopoietic progenitors (MPPs) emerge independently from HE, with notable contributions from non-endothelial sources. This review explores the spatiotemporal heterogeneity of HE and discusses how this diversity contributes to the emergence of HSPCs. We propose an integrated framework that refines current models by highlighting the regional and temporal variations in HE that drive HSPC diversification. By synthesizing current knowledge, this review offers novel insights into the origins of hematopoietic diversity and the factors that govern HE differentiation.