Single-cell fate decisions of bipotential hematopoietic progenitors.
Brand M., Morrissey E.
PURPOSE OF REVIEW: In hematopoiesis, rapid cell fate decisions are necessary for timely responses to environmental stimuli resulting in the production of diverse types of blood cells. Early studies have led to a hierarchical, tree-like view of hematopoiesis with hematopoietic stem cells residing at the apex and serially branching out to give rise to bipotential progenitors with increasingly restricted lineage potential. Recent single-cell studies have challenged some aspects of the classical model of hematopoiesis. Here, we review the latest articles on cell fate decision in hematopoietic progenitors, highlighting single-cell studies that have questioned previously established concepts and those that have reaffirmed them. RECENT FINDINGS: The hierarchical organization of hematopoiesis and the importance of transcription factors have been largely validated at the single-cell level. In contrast, single-cell studies have shown that lineage commitment is progressive rather than switch-like as originally proposed. Furthermore, the reconstruction of cell fate paths suggested the existence of a gradient of hematopoietic progenitors that are in a continuum of changing fate probabilities rather than in a static bipotential state, leading us to reconsider the notion of bipotential progenitors. SUMMARY: Single-cell transcriptomic and proteomic studies have transformed our view of lineage commitment and offer a drastically different perspective on hematopoiesis.