The Ins and the Outs of Hematopoiesis: Intrinsic and extrinsic regulators of hematopoietic stem cell fate choices
Hematopoiesis, the process of generating all blood and immune cells from hematopoietic stem cells (HSCs), is a tightly regulated process orchestrated by cell-intrinsic and cell-extrinsic cues. This process occurs in “waves” during fetal development, with windows of distinct and transient hematopoietic stem and progenitor cells (HSPCs) giving rise to “non-traditional” mature cell types. These cells are referred to as non-traditional because they arise during fetal development from these unique HSPCs, and then self-maintain for the lifespan without contribution from the adult (or life-long definitive) HSC pool. In contrast, adult hematopoiesis occurs in a very well-characterized hierarchy, where HSCs differentiate in a more lineage-restricted progression into more lineage restricted progenitor cells before terminally differentiating into “traditional” mature cell types. These cell types are referred to as traditional mature blood and immune cells because they are constantly replenished from the life-long definitive HSCs for the remainder of life. This body of work identifies cell-intrinsic and cell-extrinsic regulators of this process both during steady state health development and maintenance, as well as how dysregulation of this process alters hematopoietic output and function for life.