MicroRNA Expression Patterns and Function in Endodermal Differentiation of Human Embryonic Stem Cells

被引：85

作者：

Tzur, Galit ^{[1
]}

Levy, Asaf ^{[2
]}

Meiri, Eti ^{[2
]}

Barad, Omer ^{[2
]}

Spector, Yael ^{[2
]}

Bentwich, Zvi ^{[2
]}

Mizrahi, Lina ^{[1
]}

Katzenellenbogen, Mark ^{[1
]}

Ben-Shushan, Etti ^{[1
]}

Reubinoff, Benjamin E. ^{[1
]}

Galun, Eithan ^{[1
]}

机构：

[1] Hadassah Univ Hosp, Goldyne Savad Inst Gene Therapy, IL-91120 Jerusalem, Israel

[2] Rosetta Genom, Rehovot, Israel

来源：

PLOS ONE | 2008年 / 3卷 / 11期

关键词：

D O I：

10.1371/journal.pone.0003726

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background/Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

引用

页数：15

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