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Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence
A balance between quiescence and proliferation is critical for proper maintenance of the hematopoietic stem cell (HSC) pool. Although a lot is known about hematopoiesis, molecular mechanisms that control HSC quiescence remain largely unknown. The ubiquitin-editing enzyme A20 functions as a central r...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322050/ https://www.ncbi.nlm.nih.gov/pubmed/25624445 http://dx.doi.org/10.1084/jem.20132544 |
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author | Nakagawa, Masahiro Marshall Thummar, Keyur Mandelbaum, Jonathan Pasqualucci, Laura Rathinam, Chozha Vendan |
author_facet | Nakagawa, Masahiro Marshall Thummar, Keyur Mandelbaum, Jonathan Pasqualucci, Laura Rathinam, Chozha Vendan |
author_sort | Nakagawa, Masahiro Marshall |
collection | PubMed |
description | A balance between quiescence and proliferation is critical for proper maintenance of the hematopoietic stem cell (HSC) pool. Although a lot is known about hematopoiesis, molecular mechanisms that control HSC quiescence remain largely unknown. The ubiquitin-editing enzyme A20 functions as a central regulator of inflammation and adaptive immunity. Here, we show that a deficiency of A20 in the hematopoietic system causes anemia, lymphopenia, and postnatal lethality. Lack of A20 in HSCs results in diminished pool size, impaired radioprotection, defective repopulation, and loss of quiescence. A20-deficient HSCs display increased IFN-γ signaling, caused by augmented NF-κB activation. Strikingly, deletion of both IFN-γ and A20 in hematopoietic cells results in partial rescue of the HSC phenotype. We anticipate that our experiments will facilitate the understanding of mechanisms through which A20-mediated inflammatory signals control HSC quiescence and functions. |
format | Online Article Text |
id | pubmed-4322050 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43220502015-08-09 Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence Nakagawa, Masahiro Marshall Thummar, Keyur Mandelbaum, Jonathan Pasqualucci, Laura Rathinam, Chozha Vendan J Exp Med Article A balance between quiescence and proliferation is critical for proper maintenance of the hematopoietic stem cell (HSC) pool. Although a lot is known about hematopoiesis, molecular mechanisms that control HSC quiescence remain largely unknown. The ubiquitin-editing enzyme A20 functions as a central regulator of inflammation and adaptive immunity. Here, we show that a deficiency of A20 in the hematopoietic system causes anemia, lymphopenia, and postnatal lethality. Lack of A20 in HSCs results in diminished pool size, impaired radioprotection, defective repopulation, and loss of quiescence. A20-deficient HSCs display increased IFN-γ signaling, caused by augmented NF-κB activation. Strikingly, deletion of both IFN-γ and A20 in hematopoietic cells results in partial rescue of the HSC phenotype. We anticipate that our experiments will facilitate the understanding of mechanisms through which A20-mediated inflammatory signals control HSC quiescence and functions. The Rockefeller University Press 2015-02-09 /pmc/articles/PMC4322050/ /pubmed/25624445 http://dx.doi.org/10.1084/jem.20132544 Text en © 2015 Nakagawa et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Nakagawa, Masahiro Marshall Thummar, Keyur Mandelbaum, Jonathan Pasqualucci, Laura Rathinam, Chozha Vendan Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence |
title | Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence |
title_full | Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence |
title_fullStr | Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence |
title_full_unstemmed | Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence |
title_short | Lack of the ubiquitin-editing enzyme A20 results in loss of hematopoietic stem cell quiescence |
title_sort | lack of the ubiquitin-editing enzyme a20 results in loss of hematopoietic stem cell quiescence |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322050/ https://www.ncbi.nlm.nih.gov/pubmed/25624445 http://dx.doi.org/10.1084/jem.20132544 |
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