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Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow
Hematopoietic stem and progenitor cells (HSPCs) undergo self-renewal and differentiation to guarantee a constant supply of short-lived blood cells. Both intrinsic and extrinsic factors determine HSPC fate, but the underlying mechanisms remain elusive. Here, we report that Proteinase 3 (PR3), a serin...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235012/ https://www.ncbi.nlm.nih.gov/pubmed/30392974 http://dx.doi.org/10.1016/j.stemcr.2018.10.004 |
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author | Karatepe, Kutay Zhu, Haiyan Zhang, Xiaoyu Guo, Rongxia Kambara, Hiroto Loison, Fabien Liu, Peng Yu, Hongbo Ren, Qian Luo, Xiao Manis, John Cheng, Tao Ma, Fengxia Xu, Yuanfu Luo, Hongbo R. |
author_facet | Karatepe, Kutay Zhu, Haiyan Zhang, Xiaoyu Guo, Rongxia Kambara, Hiroto Loison, Fabien Liu, Peng Yu, Hongbo Ren, Qian Luo, Xiao Manis, John Cheng, Tao Ma, Fengxia Xu, Yuanfu Luo, Hongbo R. |
author_sort | Karatepe, Kutay |
collection | PubMed |
description | Hematopoietic stem and progenitor cells (HSPCs) undergo self-renewal and differentiation to guarantee a constant supply of short-lived blood cells. Both intrinsic and extrinsic factors determine HSPC fate, but the underlying mechanisms remain elusive. Here, we report that Proteinase 3 (PR3), a serine protease mainly confined to granulocytes, is also expressed in HSPCs. PR3 deficiency intrinsically suppressed cleavage and activation of caspase-3, leading to expansion of the bone marrow (BM) HSPC population due to decreased apoptosis. PR3-deficient HSPCs outcompete the long-term reconstitution potential of wild-type counterparts. Collectively, our results establish PR3 as a physiological regulator of HSPC numbers. PR3 inhibition is a potential therapeutic target to accelerate and increase the efficiency of BM reconstitution during transplantation. |
format | Online Article Text |
id | pubmed-6235012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-62350122018-11-19 Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow Karatepe, Kutay Zhu, Haiyan Zhang, Xiaoyu Guo, Rongxia Kambara, Hiroto Loison, Fabien Liu, Peng Yu, Hongbo Ren, Qian Luo, Xiao Manis, John Cheng, Tao Ma, Fengxia Xu, Yuanfu Luo, Hongbo R. Stem Cell Reports Article Hematopoietic stem and progenitor cells (HSPCs) undergo self-renewal and differentiation to guarantee a constant supply of short-lived blood cells. Both intrinsic and extrinsic factors determine HSPC fate, but the underlying mechanisms remain elusive. Here, we report that Proteinase 3 (PR3), a serine protease mainly confined to granulocytes, is also expressed in HSPCs. PR3 deficiency intrinsically suppressed cleavage and activation of caspase-3, leading to expansion of the bone marrow (BM) HSPC population due to decreased apoptosis. PR3-deficient HSPCs outcompete the long-term reconstitution potential of wild-type counterparts. Collectively, our results establish PR3 as a physiological regulator of HSPC numbers. PR3 inhibition is a potential therapeutic target to accelerate and increase the efficiency of BM reconstitution during transplantation. Elsevier 2018-11-01 /pmc/articles/PMC6235012/ /pubmed/30392974 http://dx.doi.org/10.1016/j.stemcr.2018.10.004 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Karatepe, Kutay Zhu, Haiyan Zhang, Xiaoyu Guo, Rongxia Kambara, Hiroto Loison, Fabien Liu, Peng Yu, Hongbo Ren, Qian Luo, Xiao Manis, John Cheng, Tao Ma, Fengxia Xu, Yuanfu Luo, Hongbo R. Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow |
title | Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow |
title_full | Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow |
title_fullStr | Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow |
title_full_unstemmed | Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow |
title_short | Proteinase 3 Limits the Number of Hematopoietic Stem and Progenitor Cells in Murine Bone Marrow |
title_sort | proteinase 3 limits the number of hematopoietic stem and progenitor cells in murine bone marrow |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235012/ https://www.ncbi.nlm.nih.gov/pubmed/30392974 http://dx.doi.org/10.1016/j.stemcr.2018.10.004 |
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