AUTHOR=Treichel Sydney , Filippi Marie-Dominique 

TITLE=Linking cell cycle to hematopoietic stem cell fate decisions

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1231735

DOI=10.3389/fcell.2023.1231735

ISSN=2296-634X

ABSTRACT=Hematopoietic stem cells (HSCs) have the properties to self-renew and/or differentiate into any blood cell lineages. In order to balance the maintenance of the stem cell pool with supporting mature blood cell production, the fate decisions to self-renew or to commit to differentiation must be tightly controlled, as dysregulation of this process can lead to bone marrow failure or leukemogenesis. The contribution of the cell cycle to cell fate decisions has been well established in numerous types of stem cells, including pluripotent stem cells. Cell cycle length is an integral component of hematopoietic progenitor fate. HSCs must remain quiescent to prevent premature replicative exhaustion. Yet, HSCs must be activated into cycle in order to produce daughter cells that will either retain stem cell properties or commit to differentiation. How the cell cycle contributes to HSC fate decisions is emerging from recent studies. HSC functions can be stratified based on cell cycle kinetics and divisional history, suggesting a link between HSC activity and cell cycle length. HSC fate decisions are also regulated by asymmetric cell divisions and recent studies have implicated metabolic and organelle activity in regulating HSC fate. In this review, we discuss the current understanding of the mechanisms underlying HSC fate decisions and how they are linked to the cell cycle.