MicroRNA Profiling of Human-Induced Pluripotent Stem Cells

MicroRNA Profiling of Human-Induced Pluripotent Stem Cells
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DOI:
10.1089/scd.2008.0247
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发表时间:
2009-06-01
影响因子:
4
通讯作者:
Wu, Joseph C.
Wu, Joseph C.
中科院分区:
医学3区
文献类型:
--
作者:
Wilson, Kitchener D.;Venkatasubrahmanyam, Shivkumar;Wu, Joseph C.

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MicroRNAs (miRNAs)是一种新发现的内源性小非编码rna,它通过靶向mrna进行切割或翻译抑制而发挥重要的转录后调控作用。越来越多的证据支持mirna对人类胚胎干细胞(hESC)自我更新、多能性和分化的重要性。然而,在诱导多能干细胞(iPSC)中,胚胎样细胞使用确定的因子从成人细胞重编程,mirna在重编程中的作用尚未得到很好的表征。确定与重编程相关的miRNA将对多能性所需的特定miRNA表达模式产生重要的见解。为了解决这一知识的缺乏,我们使用miRNA微阵列来比较人类多能干细胞、hESCs和胎儿成纤维细胞的“microrna组”。我们确认在iPSCs和hESCs中存在一组显著上调的mirna,如miR-302和17-92簇。我们还强调了两种多能细胞类型之间的差异,如miR-371/372/373簇的表达。除了组蛋白修饰、启动子甲基化、转录因子和其他调控控制元件外,我们认为多能细胞的这些miRNA特征可能代表了对细胞命运决定的另一层调控控制,并且应该证明对细胞重编程领域很重要。
MicroRNAs (miRNAs) are a newly discovered endogenous class of small noncoding RNAs that play important posttranscriptional regulatory roles by targeting mRNAs for cleavage or translational repression. Accumulating evidence now supports the importance of miRNAs for human embryonic stem cell (hESC) self-renewal, pluripotency, and differentiation. However, with respect to induced pluripotent stem cells (iPSC), in which embryonic-like cells are reprogrammed from adult cells using defined factors, the role of miRNAs during reprogramming has not been well-characterized. Determining the miRNAs that are associated with reprogramming should yield significant insight into the specific miRNA expression patterns that are required for pluripotency. To address this lack of knowledge, we use miRNA microarrays to compare the "microRNA-omes" of human iPSCs, hESCs, and fetal fibroblasts. We confirm the presence of a signature group of miRNAs that is up-regulated in both iPSCs and hESCs, such as the miR-302 and 17-92 clusters. We also highlight differences between the two pluripotent cell types, as in expression of the miR-371/372/373 cluster. In addition to histone modifications, promoter methylation, transcription factors, and other regulatory control elements, we believe these miRNA signatures of pluripotent cells likely represent another layer of regulatory control over cell fate decisions, and should prove important for the cellular reprogramming field.