Retinoic Acid Induces Embryonic Stem Cell Differentiation by Altering Both Encoding RNA and microRNA Expression.
Retinoic Acid Induces Embryonic Stem Cell Differentiation by Altering Both Encoding RNA and microRNA Expression.
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视黄酸通过改变编码 RNA 和 microRNA 表达来诱导胚胎干细胞分化
DOI：
10.1371/journal.pone.0132566
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Zhang J;Gao Y;Yu M;Wu H;Ai Z;Wu Y;Liu H;Du J;Guo Z;Zhang Y
视黄酸（RA）是一种维生素a代谢物，对早期胚胎发育和促进干细胞神经谱系规范至关重要；然而，RA对胚胎干细胞分化过程中mRNA转录和microRNA水平的影响尚不清楚。在这里，我们提出mRNA微阵列和microRNA高输出测序来阐明RA如何调节基因表达。通过mRNA微阵列分析，我们发现RA在激活小鼠胚胎干细胞（mESCs）外胚层标记物的同时抑制多能性相关基因。此外，RA通过改变表观遗传相关基因Dnmt3b和Dnmt3l的表达来调节mESCs的DNA甲基化。此外，H3K4me2，一种多能组蛋白修饰，被RA刺激抑制。从microRNA序列数据中，我们发现了两个下调的microRNA，即miR-200b和miR-200c，它们调节干细胞的多能性。我们发现miR-200b或miR-200c缺失抑制了多能基因的表达，包括Oct4和Nanog，并激活了外胚层标记基因Nestin的表达。这些结果表明，类维甲酸通过调节miR-200b/200c诱导mESCs分化。我们的研究结果提供了mRNA和microRNA基因网络的景观，并表明miR-200b/200c在ra诱导的mESCs分化中的关键作用。
Retinoic acid (RA) is a vitamin A metabolite that is essential for early embryonic development and promotes stem cell neural lineage specification; however, little is known regarding the impact of RA on mRNA transcription and microRNA levels on embryonic stem cell differentiation. Here, we present mRNA microarray and microRNA high-output sequencing to clarify how RA regulates gene expression. Using mRNA microarray analysis, we showed that RA repressed pluripotency-associated genes while activating ectoderm markers in mouse embryonic stem cells (mESCs). Moreover, RA modulated the DNA methylation of mESCs by altering the expression of epigenetic-associated genes such as Dnmt3b and Dnmt3l. Furthermore, H3K4me2, a pluripotent histone modification, was repressed by RA stimulation. From microRNA sequence data, we identified two downregulated microRNAs, namely, miR-200b and miR-200c, which regulated the pluripotency of stem cells. We found that miR-200b or miR-200c deficiency suppressed the expression of pluripotent genes, including Oct4 and Nanog, and activated the expression of the ectodermal marker gene Nestin. These results demonstrate that retinoid induces mESCs to differentiate by regulating miR-200b/200c. Our findings provide the landscapes of mRNA and microRNA gene networks and indicate the crucial role of miR-200b/200c in the RA-induced differentiation of mESCs.
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影响因子：
5.9
作者：
Castelo-Branco, Goncalo G;Lilja, Tobias;Wallenborg, Karolina;Falcao, Ana M.;Marques, Sueli C.;Gracias, Aileen;Solum, Derek;Paap, Ricardo;Walfridsson, Julian;Teixeira, Ana I.;Rosenfeld, Michael G.;Jepsen, Kristen;Hermanson, Ola
通讯作者：
Hermanson, Ola
影响因子：
3.7
作者：
Howe EN;Cochrane DR;Cittelly DM;Richer JK
通讯作者：
Richer JK
DOI：
10.1038/nrg3473
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian
影响因子：
5.2
作者：
Hough, Shelley R.;Clements, Ian;Wiederholt, Kristin A.
通讯作者：
Wiederholt, Kristin A.