APC/C is essential for hematopoiesis and impaired in aplastic anemia.
APC/C is essential for hematopoiesis and impaired in aplastic anemia.
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APC/C 对于造血至关重要，但在再生障碍性贫血中受损
DOI：
10.18632/oncotarget.18808
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发表时间：
2017-09-08
期刊：
影响因子：
--
通讯作者：
Chen GQ
中科院分区：
文献类型：
--
作者：
Wang J;Yin MZ;Zhao KW;Ke F;Jin WJ;Guo XL;Liu TH;Liu XY;Gu H;Yu XM;Li Z;Mu LL;Hong DL;Chen J;Chen GQ
后期促进复合体/环体 (APC/C) 对于细胞周期进展至关重要。最近，其非有丝分裂功能也被报道，但在包括造血细胞在内的多种组织中的研究较少。在这里，我们开发了一种可诱导的 Anapc2（APC/C 的核心亚基）敲除小鼠。敲除诱导后 7 天内，动物表现出致命的骨髓衰竭。他们的造血干细胞和祖细胞（HSPC）急剧下降，并且几乎无法形成集落。此外，BrdU 标记保留细胞测定结果表明，休眠的 HPSC 迅速丢失。对细胞周期调节因子 Skp2、P27、Cdk2 和 Cyclin E1 的分析表明，这些静止干细胞经历了从静止到有丝分裂的转变，然后发生凋亡。接下来，我们检测了再生障碍性贫血患者 CD34+ HSPC 中的 Anapc2 表达。骨髓中CD34+细胞明显减少，残留CD34+细胞中Anapc2表达检测不到，提示APC/C缺陷，可能与再生障碍性贫血的发病有关。
Anaphase promoting complex/cyclosome (APC/C) is essential for cell cycle progression. Recently, its non-mitotic functions were also reported but less studied in several tissues including hematopoietic cells. Here, we developed an inducible Anapc2 (a core subunit of APC/C) knockout mice. The animals displayed a fatal bone marrow failure within 7 days after knockout induction. Their hematopoietic stem and progenitor cells (HSPCs) demonstrated a sharp decline and could form little colony. Further, the results of BrdU label-retaining cell assay showed that the dormant HPSCs lost rapidly. Analysis of cell cycle regulators, Skp2, P27, Cdk2, and Cyclin E1, suggested that these quiescent stem cells underwent a shift from quiescence to mitosis followed by apoptosis. We next detected Anapc2-expression in the CD34+ HSPCs of patients with aplastic anemia. CD34+ cells were markedly decreased in the bone marrow and Anapc2-expression in the residual CD34+ cells was undetectable, suggesting that APC/C was deficient and might have a relationship with the pathogenesis of aplastic anemia.
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DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li L;Clevers H
通讯作者：
Clevers H
影响因子：
21.3
作者：
Carrano, AC;Eytan, E;Pagano, M
通讯作者：
Pagano, M
影响因子：
3.9
作者：
Manchado, Eusebio;Eguren, Manuel;Malumbres, Marcos
通讯作者：
Malumbres, Marcos
影响因子：
64.5
作者：
Wilson, Anne;Laurenti, Elisa;Trumpp, Andreas
通讯作者：
Trumpp, Andreas
影响因子：
3.3
作者：
Wu, George;Glickstein, Sara;Wan, Yong
通讯作者：
Wan, Yong