MicroRNAs are indispensable for reprogramming mouse embryonic fibroblasts into induced stem cell-like cells.
MicroRNAs are indispensable for reprogramming mouse embryonic fibroblasts into induced stem cell-like cells.
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DOI：
10.1371/journal.pone.0039239
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Choi MY
中科院分区：
文献类型：
--
作者：
Kim BM;Thier MC;Oh S;Sherwood R;Kanellopoulou C;Edenhofer F;Choi MY
microrna在细胞维持、增殖和分化中起着关键作用。它们也被认为在疾病发病机制和最近的细胞重编程中发挥关键作用。某些microRNA簇可以增强甚至直接诱导重编程，而抑制参与microRNA加工的关键蛋白会降低重编程效率。尽管microrna在细胞重编程中明显发挥着重要作用，但microrna是否绝对必要仍不清楚。我们试图通过使用一组定义的转录因子对dicer缺失的小鼠胚胎成纤维细胞（mef）进行重编程来回答这个基本问题，mef缺乏几乎所有的功能性microrna。使用慢病毒或piggyBac转座子载体将重编程因子转导到两种独立衍生的Dicer-null MEFs系中，不能产生类似胚胎干细胞（ESCs）的细胞。然而，人类Dicer在Dicer-null mef中的表达恢复了它们的重编程潜能。我们的研究首次证明了microrna对于去分化重编程是不可或缺的。
MicroRNAs play a pivotal role in cellular maintenance, proliferation, and differentiation. They have also been implicated to play a key role in disease pathogenesis, and more recently, cellular reprogramming. Certain microRNA clusters can enhance or even directly induce reprogramming, while repressing key proteins involved in microRNA processing decreases reprogramming efficiency. Although microRNAs clearly play important roles in cellular reprogramming, it remains unknown whether microRNAs are absolutely necessary. We endeavored to answer this fundamental question by attempting to reprogram Dicer-null mouse embryonic fibroblasts (MEFs) that lack almost all functional microRNAs using a defined set of transcription factors. Transduction of reprogramming factors using either lentiviral or piggyBac transposon vector into two, independently derived lines of Dicer-null MEFs failed to produce cells resembling embryonic stem cells (ESCs). However, expression of human Dicer in the Dicer-null MEFs restored their reprogramming potential. Our study demonstrates for the first time that microRNAs are indispensable for dedifferentiation reprogramming.
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