Hematopoietic Stem Cell Stress and Regeneration
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CELL:CELL INTERACTIONS IN STEM CELL MAINTENANCE (D LUCAS, SECTION EDITOR)
Hematopoietic Stem Cell Stress and Regeneration Christina M. Termini 1 & John P. Chute 1,2,3 Accepted: 30 October 2020 # Springer Nature Switzerland AG 2020
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 nichederived 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. Keywords Hematopoietic stem cell . Stress . Regeneration . Bone marrow . Microenvironment
Introduction
Mechanisms of HSC Stress
Hematopoietic stem cells (HSCs) are responsible for maintaining and regenerating the adult hematopoietic system throughout the lifetime of an individual. External and environmental stress incurred by HSCs leads to significant alterations in HSC behavior, often leading to permanent cellular and molecular consequences (Fig. 1). In this review, we will summarize how intrinsic and extrinsic mechanisms regulate the HSC response to stress and hematopoietic regeneration.
HSCs are at the top of the hematopoietic hierarchy, through which they support the maintenance and regeneration of the hematopoietic system via self-renewal and hematopoietic lineage specification [1]. HSCs primarily exist in the quiescent state [2] but are capable of entering cell cycle to generate mature hematopoietic cells to supplement hematopoietic cell turnover during homeostasis. Meanwhile, HSC activation and downstream hematopoietic cell production can occur in response to chemical and biological stressors, which will be detailed below.
This article is part of the Topical Collection on Cell:Cell Interactions in Stem Cell Maintenance * John P. Chute [email protected] 1
Division of Hematology/Oncology, Department of Medicine, UCLA, Los Angeles, CA, USA
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