Normal Hematopoiesis Is a Balancing Act of Self-Renewal and Regeneration

Cold Spring Harb Perspect Med. 2020 Dec 1;10(12):a035519. doi: 10.1101/cshperspect.a035519.


The hematopoietic system is highly organized to maintain its functional integrity and to meet lifelong organismal demands. Hematopoietic stem cells (HSCs) must balance self-renewal with differentiation and the regeneration of the blood system. It is a complex balancing act between these competing HSC functions. Although highly quiescent at steady state, HSCs become activated in response to inflammatory cytokines and regenerative challenges. This activation phase leads to many intrinsic stresses such as replicative, metabolic, and oxidative stress, which can cause functional decline, impaired self-renewal, and exhaustion of HSCs. To cope with these insults, HSCs use both built-in and emergency-triggered stress-response mechanisms to maintain homeostasis and to defend against disease development. In this review, we discuss how the hematopoietic system operates in steady state and stress conditions, what strategies are used to maintain functional integrity, and how deregulation in the balance between self-renewal and regeneration can drive malignant transformation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological
  • Cell Differentiation
  • Flow Cytometry / methods
  • Hematopoiesis / physiology*
  • Hematopoietic Cell Growth Factors / blood
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Homeostasis
  • Humans
  • Mice
  • Regeneration / physiology*


  • Antineoplastic Agents, Immunological
  • Hematopoietic Cell Growth Factors