Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells.
Aire regulates the expression of differentiation-associated genes and self-renewal of embryonic stem cells.
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DOI：
10.1016/j.bbrc.2010.03.042
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发表时间：
2010-04-02
影响因子：
3.1
通讯作者：
Zhang, Ming
中科院分区：
文献类型：
--
作者：
Gu, Bin;Zhang, Jiarong;Chen, Qi;Tao, Bo;Wang, Wei;Zhou, Yang;Chen, Liangbiao;Liu, Yusen;Zhang, Ming
胚胎干细胞（Embryonic stem cells，ESCs）是一种来源于早期胚胎的多能干细胞。ESC基因组整体上处于转录活跃状态，这使得ESC在遗传上具有高度分化潜能。然而，调控胚胎干细胞整体转录活性的转录因子还没有很好的定义。我们在这里显示，小鼠和人类胚胎干细胞表达两种转录因子，Aire和Deaf 1。先前已知Aire和Deaf 1分别在胸腺基质细胞和外周淋巴器官中起作用，它们有助于调节多种组织特异性抗原的异位表达，以建立自身免疫耐受。ESCs的分化大大降低了Aire和Deaf 1的表达，其模式与多能因子Oct4和Nanog相似。敲低小鼠胚胎干细胞中的Aire导致克隆形成效率显著降低以及细胞周期减弱，表明Aire在胚胎干细胞自我更新中起作用。此外，一些分化相关的基因，零星表达在胚胎干细胞的表达减少后，Aire敲低。这些结果表明，转录因子，如Aire和Deaf 1，发挥全球转录调控功能，可能发挥重要作用，在自我更新的ESC和维持ESC在转录过度活跃的状态。
Embryonic stem cells (ESCs) are pluripotent stem cells from early embryos. It has been well recognized that ESC genomes are maintained in a globally transcriptional hyperactive state, which genetically poised ESCs to the high differentiation potential. However, the transcription factors regulating the global transcription activities in ESCs are not well defined. We show here that mouse and human ESCs express two transcription factors, Aire and Deaf1. Previously known to function in the thymus stromal cells and peripheral lymphoid organs respectively, Aire and Deaf1 help regulate the ectopic expression of diverse tissue-specific antigens to establish self-immune tolerance. Differentiation of ESCs greatly reduced Aire and Deaf1 expression, in a pattern similar to the pluripotent factors, Oct4 and Nanog. Knockdown of Aire in mouse ESCs resulted in significantly decreased clone-forming efficiency as well as attenuated cell cycle, suggesting Aire plays a role in ESC self-renewal. In addition, some differentiation-associated genes that are sporadically expressed in ESCs were reduced in expression upon Aire knockdown. These results suggest that transcription factors such as Aire and Deaf1, which exert global transcriptional regulatory functions, may play important roles in self-renewal of ESCs and maintaining ESC in a transcriptionally hyperactive state.
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