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USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells

Self-renewal, replication, and differentiation of hematopoietic stem cells (HSCs) are regulated by cytokines produced by niche cells in fetal liver and bone marrow. HSCs must overcome stresses induced by cytokine deprivation during normal development. In this study, we found that ubiquitin-specific...

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Autores principales: Higuchi, Masaya, Kawamura, Hiroki, Matsuki, Hideaki, Hara, Toshifumi, Takahashi, Masahiko, Saito, Suguru, Saito, Kousuke, Jiang, Shuying, Naito, Makoto, Kiyonari, Hiroshi, Fujii, Masahiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161743/
https://www.ncbi.nlm.nih.gov/pubmed/27974222
http://dx.doi.org/10.1016/j.stemcr.2016.11.003
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author Higuchi, Masaya
Kawamura, Hiroki
Matsuki, Hideaki
Hara, Toshifumi
Takahashi, Masahiko
Saito, Suguru
Saito, Kousuke
Jiang, Shuying
Naito, Makoto
Kiyonari, Hiroshi
Fujii, Masahiro
author_facet Higuchi, Masaya
Kawamura, Hiroki
Matsuki, Hideaki
Hara, Toshifumi
Takahashi, Masahiko
Saito, Suguru
Saito, Kousuke
Jiang, Shuying
Naito, Makoto
Kiyonari, Hiroshi
Fujii, Masahiro
author_sort Higuchi, Masaya
collection PubMed
description Self-renewal, replication, and differentiation of hematopoietic stem cells (HSCs) are regulated by cytokines produced by niche cells in fetal liver and bone marrow. HSCs must overcome stresses induced by cytokine deprivation during normal development. In this study, we found that ubiquitin-specific peptidase 10 (USP10) is a crucial deubiquitinase for mouse hematopoiesis. All USP10 knockout (KO) mice died within 1 year because of bone marrow failure with pancytopenia. Bone marrow failure in these USP10-KO mice was associated with remarkable reductions of long-term HSCs (LT-HSCs) in bone marrow and fetal liver. Such USP10-KO fetal liver exhibited enhanced apoptosis of hematopoietic stem/progenitor cells (HSPCs) including LT-HSCs but not of lineage-committed progenitor cells. Transplantation of USP10-competent bone marrow cells into USP10-KO mice reconstituted multilineage hematopoiesis. These results suggest that USP10 is an essential deubiquitinase in hematopoiesis and functions by inhibiting apoptosis of HSPCs including LT-HSCs.
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spelling pubmed-51617432016-12-21 USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells Higuchi, Masaya Kawamura, Hiroki Matsuki, Hideaki Hara, Toshifumi Takahashi, Masahiko Saito, Suguru Saito, Kousuke Jiang, Shuying Naito, Makoto Kiyonari, Hiroshi Fujii, Masahiro Stem Cell Reports Article Self-renewal, replication, and differentiation of hematopoietic stem cells (HSCs) are regulated by cytokines produced by niche cells in fetal liver and bone marrow. HSCs must overcome stresses induced by cytokine deprivation during normal development. In this study, we found that ubiquitin-specific peptidase 10 (USP10) is a crucial deubiquitinase for mouse hematopoiesis. All USP10 knockout (KO) mice died within 1 year because of bone marrow failure with pancytopenia. Bone marrow failure in these USP10-KO mice was associated with remarkable reductions of long-term HSCs (LT-HSCs) in bone marrow and fetal liver. Such USP10-KO fetal liver exhibited enhanced apoptosis of hematopoietic stem/progenitor cells (HSPCs) including LT-HSCs but not of lineage-committed progenitor cells. Transplantation of USP10-competent bone marrow cells into USP10-KO mice reconstituted multilineage hematopoiesis. These results suggest that USP10 is an essential deubiquitinase in hematopoiesis and functions by inhibiting apoptosis of HSPCs including LT-HSCs. Elsevier 2016-12-13 /pmc/articles/PMC5161743/ /pubmed/27974222 http://dx.doi.org/10.1016/j.stemcr.2016.11.003 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Higuchi, Masaya
Kawamura, Hiroki
Matsuki, Hideaki
Hara, Toshifumi
Takahashi, Masahiko
Saito, Suguru
Saito, Kousuke
Jiang, Shuying
Naito, Makoto
Kiyonari, Hiroshi
Fujii, Masahiro
USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells
title USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells
title_full USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells
title_fullStr USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells
title_full_unstemmed USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells
title_short USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells
title_sort usp10 is an essential deubiquitinase for hematopoiesis and inhibits apoptosis of long-term hematopoietic stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161743/
https://www.ncbi.nlm.nih.gov/pubmed/27974222
http://dx.doi.org/10.1016/j.stemcr.2016.11.003
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