Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Stem Cells Int. 2014;2014:101349. doi: 10.1155/2014/101349. Epub 2014 Dec 2.
MicroRNAs are differentially expressed in cells and regulate multiple biological processes. We have been analyzing comprehensive expression patterns of microRNA in human and mouse embryonic stem and induced pluripotent stem cells. We determined microRNAs specifically expressed in these pluripotent stem cells, and miR-142-3p is one of such microRNAs. miR-142-3p is expressed at higher levels in induced pluripotent stem cells relative to fibroblasts in mice. Level of expression of miR142-3p decreased during embryoid body formation from induced pluripotent stem cells. Loss-of-function analyses of miR-142-3p suggested that miR-142-3p plays roles in the proliferation and differentiation of induced pluripotent stem cells. CpG motifs were found in the 5' genomic region of the miR-142-3p; they were highly methylated in fibroblasts, but not in undifferentiated induced pluripotent stem cells. Treating fibroblasts with 5-aza-2'-deoxycytidine increased the expression of miR-142-3p significantly and reduced methylation at the CpG sites, suggesting that the expression of miR-142-3p is suppressed by DNA methylation in fibroblasts. Luciferase analysis using various lengths of the 5' genomic region of miR142-3p indicated that CpGs in the proximal enhancer region may play roles in suppressing the expression of miR-142-3p in fibroblasts.
微小 RNA 在细胞中差异表达，并调节多种生物过程。我们一直在分析人类和小鼠胚胎干细胞和诱导多能干细胞中微小 RNA 的综合表达模式。我们确定了这些多能干细胞中特异性表达的微小 RNA，miR-142-3p 就是其中之一。miR-142-3p 在诱导多能干细胞中的表达水平高于小鼠成纤维细胞。在诱导多能干细胞形成胚状体的过程中，miR142-3p 的表达水平降低。miR-142-3p 的功能丧失分析表明，miR-142-3p 在诱导多能干细胞的增殖和分化中发挥作用。miR-142-3p 的 5' 基因组区域存在 CpG 基序；它们在成纤维细胞中高度甲基化，但在未分化的诱导多能干细胞中没有。用 5-氮杂-2'-脱氧胞苷处理成纤维细胞可显著增加 miR-142-3p 的表达，并降低 CpG 位点的甲基化，表明 miR-142-3p 的表达受成纤维细胞中 DNA 甲基化的抑制。使用 miR142-3p 的 5' 基因组区域的各种长度进行荧光素酶分析表明，近端增强子区域的 CpG 可能在抑制成纤维细胞中 miR-142-3p 的表达中发挥作用。
