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Developing a Systems-Based Understanding of Hematopoietic Stem Cell Cycle Control

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A Systems Biology Approach to Blood

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 844))

Abstract

To maintain hematologic homeostasis, hematopoietic stem cells (HSCs) undergo multiple rounds of cell division throughout their lives. Under steady-state conditions, adult HSCs are relatively quiescent and reside primarily in hypoxic bone marrow niches. In response to physiologic stimuli, normal HSCs either reenter the cell division cycle or remain in quiescence. A large body of work has focused on understanding the mechanistic underpinnings balancing differentiation against self-renewal programs in cycling HSCs. Numerous reports from genetically engineered mouse models harboring mutations in key pathways governing proliferation control, DNA damage responses, and metabolic regulation indicate the critical roles these processes play in determining HSC self-renewing versus blood-lineage-reconstituting divisions. In this chapter, we integrate these findings and highlight the cellular networks that control HSC function and fitness by regulating HSC cycling.

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Acknowledgements

This work was supported by NIH grant R01HL098608.

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Authors and Affiliations

  1. Northwestern University Feinberg School of Medicine, 303 East Superior Street, Lurie 5-115, 60611, Chicago, IL, USA

    Ka Tat Siu & Alex C. Minella MD

Authors
  1. Ka Tat Siu
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  2. Alex C. Minella MD
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Correspondence to Alex C. Minella MD .

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Editors and Affiliations

  1. Departments of Pediatrics and Cell & Molecular Biology, Northwestern University Feinberg School of Medicine and Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA

    Seth Joel Corey

  2. Department of Statistics, Rice University, Houston, Texas, USA

    Marek Kimmel

  3. Northwestern University Comprehensive Cancer Center, Evanston, Illinois, USA

    Joshua N. Leonard

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Siu, K., Minella, A. (2014). Developing a Systems-Based Understanding of Hematopoietic Stem Cell Cycle Control. In: Corey, S., Kimmel, M., Leonard, J. (eds) A Systems Biology Approach to Blood. Advances in Experimental Medicine and Biology, vol 844. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2095-2_9

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