The evolving views of hematopoiesis: from embryo to adulthood and from in vivo to in vitro.

The hematopoietic system composed of hematopoietic stem and progenitor cells (HSPCs) and their differentiated lineages serves as an ideal model to uncover generic principles of cell fate transitions. From gastrulation onwards, there successively emerge primitive hematopoiesis (that produces specialized hematopoietic cells), pro-definitive hematopoiesis (that produces lineage-restricted progenitor cells), and definitive hematopoiesis (that produces multipotent HSPCs). These nascent lineages develop in several transient hematopoietic sites and finally colonize into lifelong hematopoietic sites. The development and maintenance of hematopoietic lineages are orchestrated by cell-intrinsic gene regulatory networks and cell-extrinsic microenvironmental cues. Owing to the progressive methodology (e.g., high-throughput lineage tracing and single-cell functional and omics analyses), our understanding of the developmental origin of hematopoietic lineages and functional properties of certain hematopoietic organs has been updated; meanwhile, new paradigms to characterize rare cell types, cell heterogeneity and its causes, and comprehensive regulatory landscapes have been provided. Here, we review the evolving views of HSPC biology during developmental and postnatal hematopoiesis. Moreover, we discuss recent advances in the in vitro induction and expansion of HSPCs, with a focus on the implications for clinical applications.