RRC ID 47911
Author Higuchi M, Kawamura H, Matsuki H, Hara T, Takahashi M, Saito S, Saito K, Jiang S, Naito M, Kiyonari H, Fujii M.
Title USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells.
Journal Stem Cell Reports
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.
Volume 7(6)
Pages 1116-1129
Published 2016-12-13
DOI 10.1016/j.stemcr.2016.11.003
PII S2213-6711(16)30265-X
PMID 27974222
PMC PMC5161743
MeSH Anemia / pathology Animals Apoptosis* Bone Marrow / pathology Cell Cycle Cell Lineage Cytokines / deficiency Hematopoiesis* Hematopoietic Stem Cells / cytology* Hematopoietic Stem Cells / metabolism* Liver / cytology Liver / embryology Mice, Knockout Reactive Oxygen Species / metabolism Ubiquitin Thiolesterase / deficiency Ubiquitin Thiolesterase / metabolism*
IF 6.032
Times Cited 10
DNA material pENTR-Bsd-IRES-Usp10 WT (RDB15315) pENTR-Bsd-IRES-Usp10 77-792 (RDB15316) pENTR-Bsd-IRES-Usp10 95-792 (RDB15317) pENTR-Bsd-IRES-Usp10 C418A (RDB15318) pENTR-Bsd-IRES-GFP (RDB15319) pENTR-mUSP10 (RDB15325) CS-CMV-Bsd-IRES-Usp10 WT (RDB15320) CS-CMV-Bsd-IRES-Usp10 77-792 (RDB15321) CS-CMV-Bsd-IRES-Usp10 95-792 (RDB15322) CS-CMV-Bsd-IRES-Usp10 C418A (RDB15323) CS-CMV-Bsd-IRES-GFP (RDB15324) CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)