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The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells

Hematopoietic stem and progenitor cell (HSPC) transplantation represents a treatment option for patients with malignant and nonmalignant hematological diseases. Initial steps in transplantation involve the bone marrow homing and engraftment of peripheral blood–injected HSPCs. In recent work, we iden...

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Autores principales: Saito-Reis, Chelsea A., Marjon, Kristopher D., Pascetti, Erica M., Floren, Muskan, Gillette, Jennifer M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329911/
https://www.ncbi.nlm.nih.gov/pubmed/30133344
http://dx.doi.org/10.1091/mbc.E18-05-0305
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author Saito-Reis, Chelsea A.
Marjon, Kristopher D.
Pascetti, Erica M.
Floren, Muskan
Gillette, Jennifer M.
author_facet Saito-Reis, Chelsea A.
Marjon, Kristopher D.
Pascetti, Erica M.
Floren, Muskan
Gillette, Jennifer M.
author_sort Saito-Reis, Chelsea A.
collection PubMed
description Hematopoietic stem and progenitor cell (HSPC) transplantation represents a treatment option for patients with malignant and nonmalignant hematological diseases. Initial steps in transplantation involve the bone marrow homing and engraftment of peripheral blood–injected HSPCs. In recent work, we identified the tetraspanin CD82 as a potential regulator of HSPC homing to the bone marrow, although its mechanism remains unclear. In the present study, using a CD82 knockout (CD82KO) mouse model, we determined that CD82 modulates HSPC bone marrow maintenance, homing, and engraftment. Bone marrow characterization identified a significant decrease in the number of long-term hematopoietic stem cells in the CD82KO mice, which we linked to cell cycle activation and reduced stem cell quiescence. Additionally, we demonstrate that CD82 deficiency disrupts bone marrow homing and engraftment, with in vitro analysis identifying further defects in migration and cell spreading. Moreover, we find that the CD82KO HSPC homing defect is due at least in part to the hyperactivation of Rac1, as Rac1 inhibition rescues homing capacity. Together, these data provide evidence that CD82 is an important regulator of HSPC bone marrow maintenance, homing, and engraftment and suggest exploiting the CD82 scaffold as a therapeutic target for improved efficacy of stem cell transplants.
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spelling pubmed-63299112019-02-10 The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells Saito-Reis, Chelsea A. Marjon, Kristopher D. Pascetti, Erica M. Floren, Muskan Gillette, Jennifer M. Mol Biol Cell Articles Hematopoietic stem and progenitor cell (HSPC) transplantation represents a treatment option for patients with malignant and nonmalignant hematological diseases. Initial steps in transplantation involve the bone marrow homing and engraftment of peripheral blood–injected HSPCs. In recent work, we identified the tetraspanin CD82 as a potential regulator of HSPC homing to the bone marrow, although its mechanism remains unclear. In the present study, using a CD82 knockout (CD82KO) mouse model, we determined that CD82 modulates HSPC bone marrow maintenance, homing, and engraftment. Bone marrow characterization identified a significant decrease in the number of long-term hematopoietic stem cells in the CD82KO mice, which we linked to cell cycle activation and reduced stem cell quiescence. Additionally, we demonstrate that CD82 deficiency disrupts bone marrow homing and engraftment, with in vitro analysis identifying further defects in migration and cell spreading. Moreover, we find that the CD82KO HSPC homing defect is due at least in part to the hyperactivation of Rac1, as Rac1 inhibition rescues homing capacity. Together, these data provide evidence that CD82 is an important regulator of HSPC bone marrow maintenance, homing, and engraftment and suggest exploiting the CD82 scaffold as a therapeutic target for improved efficacy of stem cell transplants. The American Society for Cell Biology 2018-11-26 /pmc/articles/PMC6329911/ /pubmed/30133344 http://dx.doi.org/10.1091/mbc.E18-05-0305 Text en © 2018 Saito-Reis et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Saito-Reis, Chelsea A.
Marjon, Kristopher D.
Pascetti, Erica M.
Floren, Muskan
Gillette, Jennifer M.
The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells
title The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells
title_full The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells
title_fullStr The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells
title_full_unstemmed The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells
title_short The tetraspanin CD82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells
title_sort tetraspanin cd82 regulates bone marrow homing and engraftment of hematopoietic stem and progenitor cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329911/
https://www.ncbi.nlm.nih.gov/pubmed/30133344
http://dx.doi.org/10.1091/mbc.E18-05-0305
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