HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. CapitanoSingle-cell fate decisions of bipotential hematopoietic progenitorsBrand, Marjoriea,b; Morrissey, Edwardc Author Information aSprott Center for Stem Cell Research, Ottawa Hospital Research Institute bDepartment of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada cCenter for Computational Biology, Weatherall Institute of Molecular Medicine, Oxford, UK Correspondence to Marjorie Brand, Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada K1H8L6. Tel: +1 613 737 7700; e-mail: [email protected] and Edward Morrissey, Center for Computational Biology, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS, UK. Tel: +44 (0)1865 222435; e-mail: [email protected] Current Opinion in Hematology 27(4):p 232-240, July 2020. | DOI: 10.1097/MOH.0000000000000592 Buy Metrics Abstract 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.