CD74 is a regulator of hematopoietic stem cell maintenance

PLoS Biol. 2021 Mar 4;19(3):e3001121. doi: 10.1371/journal.pbio.3001121. eCollection 2021 Mar.


Hematopoietic stem and progenitor cells (HSPCs) are a small population of undifferentiated cells that have the capacity for self-renewal and differentiate into all blood cell lineages. These cells are the most useful cells for clinical transplantations and for regenerative medicine. So far, it has not been possible to expand adult hematopoietic stem cells (HSCs) without losing their self-renewal properties. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF), and its mRNA is known to be expressed in HSCs. Here, we demonstrate that mice lacking CD74 exhibit an accumulation of HSCs in the bone marrow (BM) due to their increased potential to repopulate and compete for BM niches. Our results suggest that CD74 regulates the maintenance of the HSCs and CD18 expression. Its absence leads to induced survival of these cells and accumulation of quiescent and proliferating cells. Furthermore, in in vitro experiments, blocking of CD74 elevated the numbers of HSPCs. Thus, we suggest that blocking CD74 could lead to improved clinical insight into BM transplant protocols, enabling improved engraftment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antigens, Differentiation, B-Lymphocyte / genetics*
  • Antigens, Differentiation, B-Lymphocyte / metabolism*
  • Bone Marrow Cells / metabolism
  • Bone Marrow Transplantation / methods
  • Cell Lineage
  • Female
  • Healthy Volunteers
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism*
  • Hematopoietic Stem Cells / physiology
  • Histocompatibility Antigens Class II / genetics*
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Intramolecular Oxidoreductases / metabolism
  • Macrophage Migration-Inhibitory Factors / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction


  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • Macrophage Migration-Inhibitory Factors
  • invariant chain
  • Intramolecular Oxidoreductases
  • MIF protein, human