Becker-Herman, Shirly and Rozenberg, Milena and Hillel-Karniel, Carmit and Gil-Yarom, Naama and Kramer, Mattias P. and Barak, Avital and Sever, Lital and David, Keren and Radomir, Lihi and Lewinsky, Hadas and Levi, Michal and Friedlander, Gilgi and Bucala, Richard and Peled, Amnon and Shachar, Idit and Eaves, Connie J. (2021) CD74 is a regulator of hematopoietic stem cell maintenance. PLOS Biology, 19 (3). e3001121. ISSN 1545-7885
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Abstract
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.
Item Type: | Article |
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Subjects: | Journal Eprints > Biological Science |
Depositing User: | Managing Editor |
Date Deposited: | 20 Feb 2023 06:30 |
Last Modified: | 22 May 2024 08:58 |
URI: | http://repository.journal4submission.com/id/eprint/734 |