CrxOS maintains the self-renewal capacity of murine embryonic stem cells
CrxOS maintains the self-renewal capacity of murine embryonic stem cells
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DOI：
10.1016/j.bbrc.2009.09.118
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发表时间：
2009-12-25
影响因子：
3.1
通讯作者：
Nishina, Hiroshi
中科院分区：
文献类型：
--
作者：
Saito, Ryota;Yamasaki, Tokiwa;Nishina, Hiroshi
胚胎干细胞通过自我更新来维持多能性。一些同源蛋白，包括Oct3/4和Nanog，被认为是维持ES细胞自我更新能力的关键因素。然而，这一过程背后的机制所需的其他基因仍不清楚。在这里，我们报告了通过电子分析鉴定含有同源盒的基因CrxOS，该基因在小鼠ES细胞中特异表达，对其自我更新是必不可少的。ES细胞主要表达内源性CrxOS的短亚型。使用基于多瘤的上体表达系统，我们证明了CrxOS短异构体的过表达足以维持ES细胞的未分化形态并刺激其增殖。最后，利用RNA干扰技术，我们证明了CrxOS对ES细胞的自我更新是必需的，并初步确定foxD3为CrxOS的下游靶基因。据我们所知，我们首次描述了CrxOS在ES细胞中的生理作用。(C)2009年，爱思唯尔公司出版。
Embryonic stem (ES) cells maintain pluripotency by self-renewal. Several homeoproteins, including Oct3/4 and Nanog, are known to be key factors in maintaining the self-renewal capacity of ES cells. However, other genes required for the mechanisms underlying this process are Still unclear. Here we report the identification by in silico, analysis of a homeobox-containing gene, CrxOS, that is specifically expressed in murine ES cells and is essential for their self-renewal. ES cells mainly express the short isoform of endogenous CrxOS. Using a polyoma-based episomal expression system, we demonstrate that overexpression of the CrxOS short isoform is sufficient for maintaining the undifferentiated morphology of ES cells and stimulating their proliferation. Finally, using RNA interference, we show that CrxOS is essential for the self-renewal of ES cells, and provisionally identify foxD3 as a downstream target gene of CrxOS. To our knowledge, ours is the first delineation of the physiological role of CrxOS in ES cells. (C) 2009 Published by Elsevier Inc.