Linking Cell Cycle to Hematopoietic Stem Cell Fate Decisions

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2023 Aug 30

PMID 37645247

Authors

Sydney Treichel

Marie-Dominique Filippi

Affiliations

Soon will be listed here.

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 stem cell fate. Hematopoietic stem cells must remain quiescent to prevent premature replicative exhaustion. Yet, hematopoietic stem cells 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 hematopoietic stem cell fate decisions is emerging from recent studies. Hematopoietic stem cell functions can be stratified based on cell cycle kinetics and divisional history, suggesting a link between Hematopoietic stem cells activity and cell cycle length. Hematopoietic stem cell fate decisions are also regulated by asymmetric cell divisions and recent studies have implicated metabolic and organelle activity in regulating hematopoietic stem cell fate. In this review, we discuss the current understanding of the mechanisms underlying hematopoietic stem cell fate decisions and how they are linked to the cell cycle.

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References

Hinge A, Xu J, Javier J, Mose E, Kumar S, Kapur R . p190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation. Nat Commun. 2017; 8:14382. PMC: 5309857. DOI: 10.1038/ncomms14382. View

Copley M, Beer P, Eaves C . Hematopoietic stem cell heterogeneity takes center stage. Cell Stem Cell. 2012; 10(6):690-697. DOI: 10.1016/j.stem.2012.05.006. View

Clapes T, Polyzou A, Prater P, Sagar , Morales-Hernandez A, Galvao Ferrarini M . Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration. Nat Cell Biol. 2021; 23(7):704-717. PMC: 8492473. DOI: 10.1038/s41556-021-00707-9. View

Qiu J, Papatsenko D, Niu X, Schaniel C, Moore K . Divisional history and hematopoietic stem cell function during homeostasis. Stem Cell Reports. 2014; 2(4):473-90. PMC: 3986626. DOI: 10.1016/j.stemcr.2014.01.016. View

Kadauke S, Udugama M, Pawlicki J, Achtman J, Jain D, Cheng Y . Tissue-specific mitotic bookmarking by hematopoietic transcription factor GATA1. Cell. 2012; 150(4):725-37. PMC: 3425057. DOI: 10.1016/j.cell.2012.06.038. View

Ranzoni A, Tangherloni A, Berest I, Riva S, Myers B, Strzelecka P . Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis. Cell Stem Cell. 2020; 28(3):472-487.e7. PMC: 7939551. DOI: 10.1016/j.stem.2020.11.015. View

Ho T, Warr M, Adelman E, Lansinger O, Flach J, Verovskaya E . Autophagy maintains the metabolism and function of young and old stem cells. Nature. 2017; 543(7644):205-210. PMC: 5344718. DOI: 10.1038/nature21388. View

Bogeska R, Mikecin A, Kaschutnig P, Fawaz M, Buchler-Schaff M, Le D . Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging. Cell Stem Cell. 2022; 29(8):1273-1284.e8. PMC: 9357150. DOI: 10.1016/j.stem.2022.06.012. View

Karigane D, Kobayashi H, Morikawa T, Ootomo Y, Sakai M, Nagamatsu G . p38α Activates Purine Metabolism to Initiate Hematopoietic Stem/Progenitor Cell Cycling in Response to Stress. Cell Stem Cell. 2016; 19(2):192-204. DOI: 10.1016/j.stem.2016.05.013. View

10.

Ema H, Takano H, Sudo K, Nakauchi H . In vitro self-renewal division of hematopoietic stem cells. J Exp Med. 2000; 192(9):1281-8. PMC: 2193353. DOI: 10.1084/jem.192.9.1281. View

11.

Dong S, Wang Q, Kao Y, Diaz A, Tasset I, Kaushik S . Chaperone-mediated autophagy sustains haematopoietic stem-cell function. Nature. 2021; 591(7848):117-123. PMC: 8428053. DOI: 10.1038/s41586-020-03129-z. View

12.

Schonberger K, Obier N, Romero-Mulero M, Cauchy P, Mess J, Pavlovich P . Multilayer omics analysis reveals a non-classical retinoic acid signaling axis that regulates hematopoietic stem cell identity. Cell Stem Cell. 2021; 29(1):131-148.e10. PMC: 9093043. DOI: 10.1016/j.stem.2021.10.002. View

13.

Zhu J, Thompson C . Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol. 2019; 20(7):436-450. PMC: 6592760. DOI: 10.1038/s41580-019-0123-5. View

14.

Wodarz A, Ramrath A, Grimm A, Knust E . Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J Cell Biol. 2000; 150(6):1361-74. PMC: 2150710. DOI: 10.1083/jcb.150.6.1361. View

15.

Bernitz J, Rapp K, Daniel M, Shcherbinin D, Yuan Y, Gomes A . Memory of Divisional History Directs the Continuous Process of Primitive Hematopoietic Lineage Commitment. Stem Cell Reports. 2020; 14(4):561-574. PMC: 7160360. DOI: 10.1016/j.stemcr.2020.03.005. View

16.

Lu Y, Sanada C, Xavier-Ferrucio J, Wang L, Zhang P, Grimes H . The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell Rep. 2018; 25(8):2083-2093.e4. PMC: 6336197. DOI: 10.1016/j.celrep.2018.10.084. View

17.

Hammond C, Wu S, Wang F, MacAldaz M, Eaves C . Aging alters the cell cycle control and mitogenic signaling responses of human hematopoietic stem cells. Blood. 2023; 141(16):1990-2002. DOI: 10.1182/blood.2022017174. View

18.

Westermann B . Mitochondrial inheritance in yeast. Biochim Biophys Acta. 2013; 1837(7):1039-46. DOI: 10.1016/j.bbabio.2013.10.005. View

19.

Kent D, Dykstra B, Cheyne J, Ma E, Eaves C . Steel factor coordinately regulates the molecular signature and biologic function of hematopoietic stem cells. Blood. 2008; 112(3):560-7. PMC: 2481530. DOI: 10.1182/blood-2007-10-117820. View

20.

Bradford G, Williams B, Rossi R, Bertoncello I . Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment. Exp Hematol. 1997; 25(5):445-53. View