title: USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells.
abstract: 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.
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan. Electronic address: masahigu@kanazawa-med.ac.jp.
authors.forename: Masaya
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Department of Clinical Engineering and Medical Technology, Faculty of Medical Technology, Niigata University of Health and Welfare, Niigata 950-3198, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawamura
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuki
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hara
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Saito
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Saito
authors.affiliation: Division of Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan; Niigata College of Medical Technology, Niigata 950-2076, Japan.
authors.forename: Shuying
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Division of Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.affiliation: Animal Resource Development Unit and Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan. Electronic address: fujiimas@med.niigata-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
mesh_terms: D000740:Anemia / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology; D002453:Cell Cycle; D019070:Cell Lineage; D016207:Cytokines / Q000172:deficiency; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000196:embryology; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000172:deficiency / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; C579090:USP10 protein, mouse; D043222:Ubiquitin Thiolesterase
keywords: apoptosis; hematopoietic stem cells; ubiquitin specific peptidase