USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells.
USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells.
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DOI：
10.1016/j.stemcr.2016.11.003
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发表时间：
2016-12-13
影响因子：
5.9
通讯作者：
Fujii, Masahiro
中科院分区：
文献类型：
--
作者：
Higuchi, Masaya;Kawamura, Hiroki;Matsuki, Hideaki;Hara, Toshifumi;Takahashi, Masahiko;Saito, Suguru;Saito, Kousuke;Jiang, Shuying;Naito, Makoto;Kiyonari, Hiroshi;Fujii, Masahiro
造血干细胞（hsc）的自我更新、复制和分化受胎儿肝脏和骨髓中生态位细胞产生的细胞因子的调节。造血干细胞在正常发育过程中必须克服细胞因子剥夺引起的应激。在这项研究中，我们发现泛素特异性肽酶10 （USP10）是小鼠造血过程中至关重要的去泛素酶。所有USP10基因敲除（KO）小鼠均在1年内死亡，原因是骨髓衰竭伴全血细胞减少症。这些USP10-KO小鼠的骨髓衰竭与骨髓和胎儿肝脏中长期造血干细胞（lt - hsc）的显著减少有关。这样的USP10-KO胎儿肝脏表现出造血干细胞/祖细胞（HSPCs）的凋亡增强，包括lt - hsc，但不包括谱系性祖细胞。将usp10 -能态骨髓细胞移植到USP10-KO小鼠体内，可重建多系造血功能。这些结果表明USP10是造血过程中必需的去泛素酶，并通过抑制包括lt -造血干细胞在内的造血干细胞的凋亡发挥作用。在这篇文章中，Fujii、Higuchi和同事们发现，系统性USP10基因敲除（USP10- ko）小鼠发生骨髓衰竭与长期造血干细胞（ht -HSC）的显著减少有关。USP10-KO胎儿肝细胞表现出造血干细胞/祖细胞（HSPCs）的凋亡增强，包括LT-HSCs。USP10抑制细胞因子剥夺诱导的体外HSPCs凋亡，这种抑制作用需要USP10的去泛素酶活性。
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. Systemic USP10-knockout mice develop bone marrow failure because of HSC depletion USP10 inhibits apoptosis of long-term HSCs in fetal liver USP10 inhibits cytokine deprivation-induced apoptosis of fetal liver HSPCs in vitro In this article, Fujii, Higuchi, and colleagues show that systemic USP10-knockout (USP10-KO) mice develop bone marrow failure associated with marked reductions in long-term hematopoietic stem cells (LT-HSCs). USP10-KO fetal liver cells exhibit enhanced apoptosis of hematopoietic stem/progenitor cells (HSPCs) including LT-HSCs. USP10 inhibits cytokine deprivation-induced apoptosis of HSPCs in vitro, and this inhibition requires the deubiquitinase activity of USP10.
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