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Banf1 对于维持小鼠和人类胚胎干细胞的自我更新是必需的。

Banf1 is required to maintain the self-renewal of both mouse and human embryonic stem cells.

机构信息

Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.

出版信息

J Cell Sci. 2011 Aug 1;124(Pt 15):2654-65. doi: 10.1242/jcs.083238. Epub 2011 Jul 12.

Abstract

Self-renewal is a complex biological process necessary for maintaining the pluripotency of embryonic stem cells (ESCs). Recent studies have used global proteomic techniques to identify proteins that associate with the master regulators Oct4, Nanog and Sox2 in ESCs or in ESCs during the early stages of differentiation. Through an unbiased proteomic screen, Banf1 was identified as a Sox2-associated protein. Banf1 has been shown to be essential for worm and fly development but, until now, its role in mammalian development and ESCs has not been explored. In this study, we examined the effect of knocking down Banf1 on ESCs. We demonstrate that the knockdown of Banf1 promotes the differentiation of mouse ESCs and decreases the survival of both mouse and human ESCs. For mouse ESCs, we demonstrate that knocking down Banf1 promotes their differentiation into cells that exhibit markers primarily associated with mesoderm and trophectoderm. Interestingly, knockdown of Banf1 disrupts the survival of human ESCs without significantly reducing the expression levels of the master regulators Sox2, Oct4 and Nanog or inducing the expression of markers of differentiation. Furthermore, we determined that the knockdown of Banf1 alters the cell cycle distribution of both human and mouse ESCs by causing an uncharacteristic increase in the proportion of cells in the G2-M phase of the cell cycle.

摘要

自我更新是维持胚胎干细胞(ESCs)多能性所必需的复杂生物学过程。最近的研究使用全局蛋白质组学技术来鉴定与 ESC 中的主调控因子 Oct4、Nanog 和 Sox2 相关的蛋白质,或在 ESC 早期分化过程中与它们相关的蛋白质。通过无偏蛋白质组学筛选,发现 Banf1 是 Sox2 相关蛋白。Banf1 被证明对蠕虫和苍蝇的发育至关重要,但直到现在,其在哺乳动物发育和 ESCs 中的作用尚未被探索。在这项研究中,我们研究了敲低 Banf1 对 ESCs 的影响。我们证明,敲低 Banf1 促进了小鼠 ESCs 的分化,并降低了小鼠和人 ESCs 的存活率。对于小鼠 ESCs,我们证明敲低 Banf1 促进其分化为主要表现为中胚层和滋养外胚层特征的细胞。有趣的是,敲低 Banf1 破坏了人 ESCs 的存活,而没有显著降低主调控因子 Sox2、Oct4 和 Nanog 的表达水平,也没有诱导分化标志物的表达。此外,我们确定敲低 Banf1 通过导致细胞周期中 G2-M 期细胞比例的特征性增加,改变了人 ESC 和鼠 ESC 的细胞周期分布。

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Role of SOX2 in maintaining pluripotency of human embryonic stem cells.SOX2 在维持人类胚胎干细胞多能性中的作用。
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