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PMID: 19015728 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

MicroRNA expression patterns and function in endodermal differentiation of human embryonic stem cells.

PloS one ·Vol. 3 ·No. 11 ·2008-00-00 ·Pages e3726

Tzur G, Levy A, Meiri E, Barad O, Spector Y, Bentwich Z, Mizrahi L, Katzenellenbogen M, Ben-Shushan E, Reubinoff BE, Galun E

Abstract

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.

MeSH Terms
Algorithms Cell Differentiation Cell Line Embryonic Stem Cells/cytology Endoderm/metabolism Flow Cytometry Gene Expression Profiling Genetic Vectors Genome, Human Humans MicroRNAs/genetics Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Sodium Oxybate/pharmacology Transcription Factors/metabolism
Chemicals
MicroRNAs Transcription Factors Sodium Oxybate
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Tzur Galit
Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
Levy Asaf
Meiri Eti
Barad Omer
Spector Yael
Bentwich Zvi
Mizrahi Lina
Katzenellenbogen Mark
Ben-Shushan Etti
Reubinoff Benjamin E
Galun Eithan
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0003726
Published
2008-00-00
Epub
2008-00-18
Pages
e3726
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2581805
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0003726 PMC Full Text View journal details
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