Aire Promotes the Self-Renewal of Embryonic Stem Cells Through Lin28
Aire Promotes the Self-Renewal of Embryonic Stem Cells Through Lin28
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Aire 通过 Lin28 促进胚胎干细胞的自我更新
DOI：
10.1089/scd.2012.0097
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发表时间：
2012-10-01
影响因子：
4
通讯作者：
Zhang Ming
中科院分区：
文献类型：
--
作者：
Gu Bin;Zhang Jiarong;Zhang Ming
自身免疫调节因子（Aire）是自身免疫中最具特征的分子之一，但其在免疫系统外的功能在很大程度上是未知的。最近发现的Aire在干细胞和早期胚胎细胞中的表达及其在胚胎干细胞（ES）自我更新中的功能突出了Aire在这些细胞中的重要性。在这项研究中，我们提出的证据表明，Aire促进多能因子Lin 28的表达和ES细胞的自我更新。我们提出了let-7 microRNA家族有助于Aire对ES细胞的自我更新促进作用的第一个证据。此外，我们发现，Aire和Lin 28在生殖嵴，卵母细胞和卵裂期胚胎中共表达，Lin 28的表达水平与Aire的表达水平相关。虽然它被广泛认为是一种混杂的基因表达激活剂，但这些结果表明，Aire通过一种特定的途径促进ES细胞的自我更新（即，Lin 28的激活和let-7 microRNA家族的抑制）。Aire和Lin 28在生殖细胞和早期胚胎中表达之间的相关性表明Aire在全能和多能干细胞中的体内功能。这项研究提出了第一个将Aire纳入多能性网络的分子途径。此外，它提供了第一个证据表明microRNA有助于Aire的调节功能，并强调了Aire在干细胞生物学和生殖中的新功能。这些功能揭示了新的观点，研究背后的分子机制的建立和维持多能性的身份。
Autoimmune regulator (Aire) is one of the most well-characterized molecules in autoimmunity, but its function outside the immune system is largely unknown. The recent discovery of Aire expression in stem cells and early embryonic cells and its function in the self-renewal of embryonic stem (ES) cells highlight the importance of Aire in these cells. In this study, we present evidence that Aire promotes the expression of the pluripotent factor Lin28 and the self-renewal of ES cells. We presented the first evidence that the let-7 microRNA family contributed to the self-renewal promoting effect of Aire on ES cells. Moreover, we showed that Aire and Lin28 are co-expressed in the genital ridge, oocytes, and cleavage-stage embryos, and the expression level of Lin28 is correlated with the expression level of Aire. Although it is widely considered to be a promiscuous gene expression activator, these results indicated that Aire promotes the self-renewal of ES cells through a specific pathway (i.e., the activation of Lin28 and the inhibition of the let-7 microRNA family). The correlation between Aire and Lin28 expression in germ cells and early embryos indicated an in vivo function for Aire in toti- and pluripotent stem cells. This study presents the first molecular pathway that incorporates Aire into the pluripotency network. Moreover, it presents the first evidence that microRNAs contribute to the regulatory function of Aire and highlights a novel function of Aire in stem cell biology and reproduction. These functions reveal novel perspectives for studying the molecular mechanisms behind the establishment and sustenance of pluripotent identity.