Hematopoietic Stem Cell Stress and Regeneration

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. 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. 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.