IRF7 suppresses hematopoietic regeneration under stress via CXCR4

Stem Cells. 2021 Feb;39(2):183-195. doi: 10.1002/stem.3308. Epub 2020 Dec 9.

Abstract

Hematopoietic stem cells (HSCs) maintain quiescence under steady state; however, they are compelled to proliferate and expand to replenish the blood system under stress. The molecular basis underlying stress hematopoiesis remains to be fully understood. In this study, we reported that IRF7 represents an important regulator of stress hematopoiesis. Interferon regulatory factor 7 (IRF7) was dispensable for normal hematopoiesis, whereas its deficiency significantly enhanced hematopoietic stem and progenitor cells (HSPCs) regeneration and improved long-term repopulation of HSCs under stress. Mechanistic studies showed that CXCR4 was identified as a downstream target of IRF7. Overexpression of CXCR4 abrogated the enhanced proliferation and regeneration of IRF7-deficient HSPCs under stress. Similar results were obtained in HSCs from human umbilical cord blood. These observations demonstrated that IRF7 plays an important role in hematopoietic regeneration under stress.

Keywords: CXCR4; hematopoietic stem and progenitor cells; hematopoietic stress; human umbilical cord blood; interferon regulatory factor 7; regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cord Blood Stem Cell Transplantation / methods*
  • Fetal Blood / metabolism
  • Fetal Blood / transplantation
  • Hematopoiesis / physiology*
  • Humans
  • Interferon Regulatory Factor-7 / antagonists & inhibitors
  • Interferon Regulatory Factor-7 / genetics
  • Interferon Regulatory Factor-7 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidative Stress / physiology*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*

Substances

  • CXCR4 protein, mouse
  • Interferon Regulatory Factor-7
  • Irf7 protein, mouse
  • Receptors, CXCR4