Argonaute-2-null embryonic stem cells are retarded in self-renewal and differentiation

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• 作者：P Chandra Shekar ; Adnan Naim ; D Partha Sarathi ; Satish Kumar
• 关键词：Argonaute 2 ; differentiation ; ES cells ; pluripotency ; RNAi
• 刊名：Journal of Biosciences
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：36
• 期：4
• 页码：649-657
• 全文大小：
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• 作者单位：P Chandra Shekar (1) (2)
  Adnan Naim (1)
  D Partha Sarathi (1)
  Satish Kumar (1)
  
  1. Centre for Cellular and Molecular Biology, CSIR, Hyderabad, 500 007, India
  2. Present address: Institute of Stem Cells and Regenerative Medicine, Bangalore, India
  
• 刊物类别：Life Sciences, general; Biomedicine general; Zoology; Plant Sciences; Microbiology; Cell Biology;
• 刊物主题：Life Sciences, general; Biomedicine general; Zoology; Plant Sciences; Microbiology; Cell Biology;
• 出版者：Springer India
• ISSN：0973-7138

文摘

RNA interference (RNAi) pathways regulate self-renewal and differentiation of embryonic stem (ES) cells. Argonaute 2 (Ago2) is a vital component of RNA-induced silencing complex (RISC) and the only Ago protein with slicer activity. We generated Ago2-deficient ES cells by conditional gene targeting. Ago2-deficient ES cells are defective in the small-RNA-mediated gene silencing and are significantly compromised in biogenesis of mature microRNA. The self-renewal rate of Ago2-deficient ES cells is affected due to failure of silencing of Cdkn1a by ES-cell-specific microRNAs (miRNA) in the absence of Ago2. Interestingly, unlike Dicer- and Dgcr8-deficient ES cells, they differentiate to all three germ layers both in vivo and in vitro. However, early differentiation of Ago2-deficient ES cells is delayed by 2鈥? days as indicated by persistence of higher levels of self-renewal/ pluripotency markers during differentiation. Further, appearance of morphological and differentiation markers is also delayed during the differentiation. In this study we show that Ago2 is essential for normal self-renewal and differentiation. Also, our data suggest that self-renewal and differentiation of ES cells are regulated by both siRNA and miRNA pathways. Keywords Argonaute 2 differentiation ES cells pluripotency RNAi