CD38 promotes hematopoietic stem cell dormancy.

Autor: Ibneeva L; Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Singh SP; IRIBHM, Université Libre de Bruxelles (ULB), Brussels, Belgium., Sinha A; Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Eski SE; IRIBHM, Université Libre de Bruxelles (ULB), Brussels, Belgium., Wehner R; Institute for Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Rupp L; Institute for Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., Kovtun I; Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Pérez-Valencia JA; Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Gerbaulet A; Institute for Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., Reinhardt S; DRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany., Wobus M; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Medical Clinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., von Bonin M; Medical Clinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., Sancho J; Instituto de Parasitología y Biomedicina 'López-Neyra' CSIC, Granada, Spain., Lund F; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America., Dahl A; DRESDEN-concept Genome Center, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany., Schmitz M; Institute for Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Bornhäuser M; National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Medical Clinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany., Chavakis T; Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Wielockx B; Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.; Experimental Center, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany., Grinenko T; Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Jiao Tong University School of Medicine, Shanghai, China.
Jazyk: angličtina
Zdroj: PLoS biology [PLoS Biol] 2024 Feb 29; Vol. 22 (2), pp. e3002517. Date of Electronic Publication: 2024 Feb 29 (Print Publication: 2024).
DOI: 10.1371/journal.pbio.3002517
Abstrakt: A subpopulation of deeply quiescent, so-called dormant hematopoietic stem cells (dHSCs) resides at the top of the hematopoietic hierarchy and serves as a reserve pool for HSCs. The state of dormancy protects the HSC pool from exhaustion throughout life; however, excessive dormancy may prevent an efficient response to hematological stresses. Despite the significance of dHSCs, the mechanisms maintaining their dormancy remain elusive. Here, we identify CD38 as a novel and broadly applicable surface marker for the enrichment of murine dHSCs. We demonstrate that cyclic adenosine diphosphate ribose (cADPR), the product of CD38 cyclase activity, regulates the expression of the transcription factor c-Fos by increasing the release of Ca2+ from the endoplasmic reticulum (ER). Subsequently, we uncover that c-Fos induces the expression of the cell cycle inhibitor p57Kip2 to drive HSC dormancy. Moreover, we found that CD38 ecto-enzymatic activity at the neighboring CD38-positive cells can promote human HSC quiescence. Together, CD38/cADPR/Ca2+/c-Fos/p57Kip2 axis maintains HSC dormancy. Pharmacological manipulations of this pathway can provide new strategies to improve the success of stem cell transplantation and blood regeneration after injury or disease.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Ibneeva 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.)
Databáze: MEDLINE
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