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Hematopoietic Stem Cell Stress and Regeneration

  • Cancer and Stem Cells (MD Filippi, Section Editor)
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Abstract

Purpose of Review

Hematopoietic stem cells (HSCs) propagate the hematopoietic system throughout the lifetime of an individual. Beyond homeostatic regulation, HSCs respond to many stressors, including infection, aging, irradiation, and chemotherapy, through distinct cellular and molecular pathways to restore homeostasis. Here, we review how HSCs and bone marrow niche cells respond to various stressors and their role in HSC regeneration.

Recent Findings

In this review, we summarize the manner in which HSCs respond to different stressors via intrinsic and extrinsic, and niche-driven mechanisms to support hematopoietic regeneration. We discuss recent work defining the cellular and molecular mechanisms by which HSCs respond to various forms of stress through specific alterations in cell cycling, DNA damage repair, and cell death. We also summarize the roles of recently defined bone marrow niche cell subtypes and niche-derived factors in mediating HSC regeneration.

Summary

Stress through aging, inflammation, and myelosuppressive treatments significantly alters hematopoietic homeostasis, requiring HSCs to quickly respond to restore order. In the event that an inadequate HSC response occurs, patients are at risk for life-threatening complications such as hemorrhage, infection and bone marrow failure. In this review, we summarize recent work defining how HSCs respond to stress and the role of the bone marrow niche in HSC regeneration.

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Funding

This work was supported by funding from the NIAID AI107333 (JPC), NIAID AI067769 (JPC), the CIRM Leadership Award LA1-08014 (JPC), the Damon Runyon Cancer Foundation DRG-2327-18 (CMT), the Burroughs Wellcome Fund PDEP #1018686 (CMT), and the UC President’s Postdoctoral Fellowship (CMT).

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  1. Division of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, CA, USA

    Christina M. Termini & John P. Chute

  2. Broad Stem Cell Research Center, UCLA, Los Angeles, CA, USA

    John P. Chute

  3. Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA

    John P. Chute

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  1. Christina M. Termini
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  2. John P. Chute
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CMT and JPC wrote the paper; CMT developed the figures.

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Correspondence to John P. Chute.

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Termini, C.M., Chute, J.P. Hematopoietic Stem Cell Stress and Regeneration. Curr Stem Cell Rep 6, 134–143 (2020). https://doi.org/10.1007/s40778-020-00181-3

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