A RHO Small GTPase Regulator ABR Secures Mitotic Fidelity in Human Embryonic Stem Cells.
A RHO Small GTPase Regulator ABR Secures Mitotic Fidelity in Human Embryonic Stem Cells.
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RHO 小型 GTP 酶调节剂 ABR 可确保人胚胎干细胞有丝分裂的保真度。
DOI：
10.1016/j.stemcr.2017.05.003
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发表时间：
2017-07-11
影响因子：
5.9
通讯作者：
Sasai Y
中科院分区：
文献类型：
--
作者：
Ohgushi M;Minaguchi M;Eiraku M;Sasai Y
多能干细胞可以在保持遗传完整性的同时进行重复的自我更新，但在长期培养过程中偶尔会获得非整倍体，这是人类多能干细胞医学应用的实际障碍。在这项研究中，我们探讨了ABR的生物学作用，RHO家族小GTP酶的调节剂，并发现它在人类胚胎干细胞（hESCs）的有丝分裂过程中具有关键作用。虽然ABR已被证明参与解离诱导的hESC凋亡，但它似乎对细胞存活没有直接影响，除非细胞-细胞接触受损。相反，我们发现这对忠实的hESC分裂很重要。从机制上讲，ABR缺失会损害中心体动力学，并使细胞容易发生染色体错位和错误分离，从而提高非整倍体的频率。这些结果为支持自我更新hESC遗传完整性的机制提供了见解。ABR缺失导致hESC中G2/M积累ABR缺失时中心体动力学和有丝分裂保真度受损当有丝分裂在没有ABR的情况下进行时，hESC显示出高的非整倍体发生率ABR在hESC分裂期间保护忠实的染色体遗传。在这篇文章中，Ohgushi和同事报告说，hESC中ABR缺失导致几个有丝分裂过程中的严重缺陷，包括中心体分离和染色体排列/分离。重要的是，ABR缺陷增加了非整倍体的频率，突出了其在赋予自我更新hESC的遗传信息的可靠遗传方式中的关键作用。
Pluripotent stem cells can undergo repeated self-renewal while retaining genetic integrity, but they occasionally acquire aneuploidy during long-term culture, which is a practical obstacle for medical applications of human pluripotent stem cells. In this study, we explored the biological roles of ABR, a regulator of RHO family small GTPases, and found that it has pivotal roles during mitotic processes in human embryonic stem cells (hESCs). Although ABR has been shown to be involved in dissociation-induced hESC apoptosis, it does not appear to have direct effects on cell survival unless cell-cell contact is impaired. Instead, we found that it is important for faithful hESC division. Mechanistically, ABR depletion compromised centrosome dynamics and predisposed the cell to chromosome misalignment and missegregation, which raised the frequency of aneuploidy. These results provide insights into the mechanisms that support the genetic integrity of self-renewing hESCs. ABR depletion leads to G2/M accumulation in hESCs Centrosome dynamics and mitotic fidelity are compromised upon ABR depletion When mitosis progresses without ABR, hESCs show a high incidence of aneuploidy ABR safeguards faithful chromosome inheritance during hESC division In this article, Ohgushi and colleagues report that ABR depletion in hESCs causes severe defects in several mitotic processes, including centrosome separation and chromosome alignment/segregation. Importantly, ABR deficiency increases the frequency of aneuploidy, highlighting its key role in conferring robust way to faithful inheritance of genetic information on self-renewing hESCs.
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影响因子：
64.5
作者：
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