MicroRNA and gene expression patterns in the differentiation of human embryonic stem cells

Jiaqiang Ren, Ping Jin, Ena Wang, Francesco M. Marincola, David F. Stroncek

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Background: The unique features of human embryonic stem (hES) cells make them the best candidate resource for both cell replacement therapy and development research. However, the molecular mechanisms responsible for the simultaneous maintenance of their self-renewal properties and undifferentiated state remain unclear. Non-coding microRNAs (miRNA) which regulate mRNA cleavage and inhibit encoded protein translation exhibit temporal or tissue-specific expression patterns and they play an important role in development timing. Results: In this study, we analyzed miRNA and gene expression profiles among samples from 3 hES cell lines (H9, I6 and BG01v), differentiated embryoid bodies (EB) derived from H9 cells at different time points, and 5 adult cell types including Human Microvascular Endothelial Cells (HMVEC), Human Umbilical Vein Endothelial Cells (HUVEC), Umbilical Artery Smooth Muscle Cells (UASMC), Normal Human Astrocytes (NHA), and Lung Fibroblasts (LFB). This analysis rendered 104 miRNAs and 776 genes differentially expressed among the three cell types. Selected differentially expressed miRNAs and genes were further validated and confirmed by quantitative real-time-PCR (qRT-PCR). Especially, members of the miR-302 cluster on chromosome 4 and miR-520 cluster on chromosome 19 were highly expressed in undifferentiated hES cells. MiRNAs in these two clusters displayed similar expression levels. The members of these two clusters share a consensus 7-mer seed sequence and their targeted genes had overlapping functions. Among the targeted genes, genes with chromatin structure modification function are enriched suggesting a role in the maintenance of chromatin structure. We also found that the expression level of members of the two clusters, miR-520b and miR-302c, were negatively correlated with their targeted genes based on gene expression analysis Conclusion: We identified the expression patterns of miRNAs and gene transcripts in the undifferentiation of human embryonic stem cells; among the miRNAs that are highly expressed in undifferentiated embryonic stem cells, the miR-520 cluster may be closely involved in hES cell function and its relevance to chromatin structure warrants further study.

Original languageEnglish
Article number20
JournalJournal of Translational Medicine
Volume7
DOIs
Publication statusPublished - 23 Mar 2009
Externally publishedYes

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Stem cells
MicroRNAs
Gene expression
Genes
Gene Expression
Chromatin
Endothelial cells
Chromosomes
Overlapping Genes
Embryoid Bodies
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 4
Umbilical Arteries
Human Umbilical Vein Endothelial Cells
Protein Biosynthesis
Embryonic Stem Cells
Cell- and Tissue-Based Therapy
Transcriptome
Astrocytes
Fibroblasts

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

MicroRNA and gene expression patterns in the differentiation of human embryonic stem cells. / Ren, Jiaqiang; Jin, Ping; Wang, Ena; Marincola, Francesco M.; Stroncek, David F.

In: Journal of Translational Medicine, Vol. 7, 20, 23.03.2009.

Research output: Contribution to journalArticle

Ren, Jiaqiang ; Jin, Ping ; Wang, Ena ; Marincola, Francesco M. ; Stroncek, David F. / MicroRNA and gene expression patterns in the differentiation of human embryonic stem cells. In: Journal of Translational Medicine. 2009 ; Vol. 7.
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