TY - JOUR
T1 - CD74 is a regulator of hematopoietic stem cell maintenance
AU - Becker-Herman, Shirly
AU - Rozenberg, Milena
AU - Hillel-Karniel, Carmit
AU - Gil-Yarom, Naama
AU - Kramer, Mattias
AU - Barak, Avital
AU - Sever, Lital
AU - David, Keren
AU - Radomir, Lihi
AU - Lewinsky, Hadas
AU - Levi, Michal
AU - Friedlander, Gilgi
AU - Bucala, Richard
AU - Peled, Amnon
AU - Shachar, Idit
N1 - Publisher Copyright:
© 2021 Becker-Herman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/3/4
Y1 - 2021/3/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85102651602&partnerID=8YFLogxK
U2 - 10.1371/journal.pbio.3001121
DO - 10.1371/journal.pbio.3001121
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C2 - 33661886
AN - SCOPUS:85102651602
SN - 1544-9173
VL - 19
JO - PLoS Biology
JF - PLoS Biology
IS - 3
M1 - e3001121
ER -
