MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells.
MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells.
复制标题
DOI：
10.1371/journal.pone.0003726
复制
发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Galun E
中科院分区：
文献类型：
--
作者：
Tzur G;Levy A;Meiri E;Barad O;Spector Y;Bentwich Z;Mizrahi L;Katzenellenbogen M;Ben-Shushan E;Reubinoff BE;Galun E
microRNAs（miRNAs）是一类在转录后调控同源mRNA的非编码小RNA。人类胚胎干细胞（human embryonic stem cells，hESC）具有多能性和自我更新的特性，可作为研究miRNAs在人类早期发育中作用的模型。我们的目的是确定内胚层分化的hESC是否表现出独特的miRNA表达模式，以及内胚层特异性miRNA的过表达是否会影响hESC的分化。利用微阵列和定量RT-PCR分析了未分化和丁酸钠诱导分化的两种hESC中miRNA的表达。然后，使用全基因组基因微阵列分析基于慢病毒的肝脏特异性miR-122过表达对hESC分化的影响。miRNA谱显示三种新的miRNA在未分化和分化的hESC中表达。在丁酸钠诱导后，两种细胞系共有的两种上调最多的miRNA是miR-24和miR-10a，其靶基因已显示出抑制内胚层分化。此外，在诱导内胚层基因表达的同时，还观察到了几种肝脏富集的miRNA，包括miR-122和miR-192。miR-122在hESC中的稳定过表达不能引导自发分化朝向明确的内胚层命运，而是延迟这些细胞的一般分化。我们的研究结果表明，特定的miRNAs的表达与分化后的特定基因的表达相关，并突出了miRNAs在hESC内胚层分化中的潜在作用。
microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs post-transcriptionally. Human embryonic stem cells (hESC), which exhibit the characteristics of pluripotency and self-renewal, may serve as a model to study the role of miRNAs in early human development. We aimed to determine whether endodermally-differentiated hESC demonstrate a unique miRNA expression pattern, and whether overexpression of endoderm-specific miRNA may affect hESC differentiation. miRNA expression was profiled in undifferentiated and NaButyrate-induced differentiated hESC of two lines, using microarray and quantitative RT-PCR. Then, the effect of lentiviral-based overexpression of liver-specific miR-122 on hESC differentiation was analyzed, using genomewide gene microarrays. The miRNA profiling revealed expression of three novel miRNAs in undifferentiated and differentiated hESC. Upon NaButyrate induction, two of the most upregulated miRNAs common to both cell lines were miR-24 and miR-10a, whose target genes have been shown to inhibit endodermal differentiation. Furthermore, induction of several liver-enriched miRNAs, including miR-122 and miR-192, was observed in parallel to induction of endodermal gene expression. Stable overexpression of miR-122 in hESC was unable to direct spontaneous differentiation towards a clear endodermal fate, but rather, delayed general differentiation of these cells. Our results demonstrate that expression of specific miRNAs correlates with that of specific genes upon differentiation, and highlight the potential role of miRNAs in endodermal differentiation of hESC.
登录
查看更多内容
影响因子：
30.8
作者：
Bentwich, I;Avniel, A;Bentwich, Z
通讯作者：
Bentwich, Z
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L
影响因子：
5.2
作者：
Jiang, Jianjie;Au, Melinda;Majumdar, Anish S.
通讯作者：
Majumdar, Anish S.
影响因子：
2.5
作者：
Chen, Caifu;Ridzon, Dana;Strauss, William M.
通讯作者：
Strauss, William M.
影响因子：
5.3
作者：
Hamazaki, Takashi;Kehoe, Sarah M.;Terada, Naohiro
通讯作者：
Terada, Naohiro