MicroRNA Profiling of Human-Induced Pluripotent Stem Cells

Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stem cells and development (Impact Factor: 3.73). 02/2009; 18(5):749-58. DOI: 10.1089/scd.2008.0247
Source: PubMed

ABSTRACT MicroRNAs (miRNAs) are a newly discovered endogenous class of small noncoding RNAs that play important posttranscriptional regulatory roles by targeting mRNAs for cleavage or translational repression. Accumulating evidence now supports the importance of miRNAs for human embryonic stem cell (hESC) self-renewal, pluripotency, and differentiation. However, with respect to induced pluripotent stem cells (iPSC), in which embryonic-like cells are reprogrammed from adult cells using defined factors, the role of miRNAs during reprogramming has not been well-characterized. Determining the miRNAs that are associated with reprogramming should yield significant insight into the specific miRNA expression patterns that are required for pluripotency. To address this lack of knowledge, we use miRNA microarrays to compare the "microRNA-omes" of human iPSCs, hESCs, and fetal fibroblasts. We confirm the presence of a signature group of miRNAs that is up-regulated in both iPSCs and hESCs, such as the miR-302 and 17-92 clusters. We also highlight differences between the two pluripotent cell types, as in expression of the miR-371/372/373 cluster. In addition to histone modifications, promoter methylation, transcription factors, and other regulatory control elements, we believe these miRNA signatures of pluripotent cells likely represent another layer of regulatory control over cell fate decisions, and should prove important for the cellular reprogramming field.

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Available from: Kitchener D Wilson, Sep 28, 2015
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    • "Although the functions of the majority of newly discovered non-coding RNAs are still unknown, some were found to play important roles in the regulation of stem cells. Recent studies concentrate on miRNAs (Wilson et al., 2009; Kim et al., 2011; Lipchina et al., 2011). In the context of stem cell biology, of particular interest is the role of these RNAs in expression of renewal genes in human embryonic stem cells (hESCs) or in regulation of induced pluripotency (Li et al., 2011). "
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    ABSTRACT: Several studies have demonstrated the important role of non-coding RNAs as regulators of posttranscriptional processes, including stem cells self-renewal and neural differentiation. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (ihPSCs) show enormous potential in regenerative medicine due to their capacity to differentiate to virtually any type of cells of human body. Deciphering the role of non-coding RNAs in pluripotency, self-renewal and neural differentiation will reveal new molecular mechanisms involved in induction and maintenances of pluripotent state as well as triggering these cells toward clinically relevant cells for transplantation. In this brief review we will summarize recently published studies which reveal the role of non-coding RNAs in pluripotency and neural differentiation of hESCs and ihPSC.
    Frontiers in Genetics 05/2014; 5:132. DOI:10.3389/fgene.2014.00132
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    • "Involvement of different miRNA clusters in the activation and inhibition of the specific cellular processes during reprogramming is presented on Figure 3. The mir-302 cluster is located in the 4q25 locus of human chromosome 4 (Puca et al. 2001) and is predominantly expressed in hES and iPS cells (Suh et al. 2004, Wilson et al. 2009), while during early embryonic development and in vitro differentiation the expression of miR-302 is lost (Suh et al. 2004, Ren et al. 2009). The majority of miR-302-targeted genes are transcripts of developmental signals and oncogenes (Lin et al. 2008). "
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    ABSTRACT: Derivation of pluripotent stem cells from adult somatic tissues by reprogramming technology has opened new therapeutic possibilities. Current most efficient procedures for derivation of induced pluripotent stem (iPS) cells are based on the viral vectors, which represent the danger of insertional mutagenesis during incorporation of introduced genes into the host genome. To circumvent this problem, the new, safe, non-integrative and non-viral strategies of reprogramming have been developed. In this review we discuss novel DNA-free and viral-free methods of reprogramming to iPS cells including protein transduction, mRNA and microRNA delivery.
    Acta neurobiologiae experimentalis 01/2014; 74(4):373-82. · 1.29 Impact Factor
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    • "One regulatory factor that has received increasing attention is miRNAs, which have the ability to regulate many target genes and control gene expression through translational repression and degradation [9]. miRNAs are expressed at different levels in a wide range of cells, including ESCs [10]–[12], iPSCs [13], and somatic cells [13]. Recent work showed that introduction of miR-302/367 resulted in higher reprogramming efficiency compared to exogenous OSKM transcription factors [5], indicating the importance of miRNAs in modulating the transition of somatic cells to pluripotent cells. "
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    ABSTRACT: Using quantitative PCR-based miRNA arrays, we comprehensively analyzed the expression profiles of miRNAs in human and mouse embryonic stem (ES), induced pluripotent stem (iPS), and somatic cells. Immature pluripotent cells were purified using SSEA-1 or SSEA-4 and were used for miRNA profiling. Hierarchical clustering and consensus clustering by nonnegative matrix factorization showed two major clusters, human ES/iPS cells and other cell groups, as previously reported. Principal components analysis (PCA) to identify miRNAs that segregate in these two groups identified miR-187, 299-3p, 499-5p, 628-5p, and 888 as new miRNAs that specifically characterize human ES/iPS cells. Detailed direct comparisons of miRNA expression levels in human ES and iPS cells showed that several miRNAs included in the chromosome 19 miRNA cluster were more strongly expressed in iPS cells than in ES cells. Similar analysis was conducted with mouse ES/iPS cells and somatic cells, and several miRNAs that had not been reported to be expressed in mouse ES/iPS cells were suggested to be ES/iPS cell-specific miRNAs by PCA. Comparison of the average expression levels of miRNAs in ES/iPS cells in humans and mice showed quite similar expression patterns of human/mouse miRNAs. However, several mouse- or human-specific miRNAs are ranked as high expressers. Time course tracing of miRNA levels during embryoid body formation revealed drastic and different patterns of changes in their levels. In summary, our miRNA expression profiling encompassing human and mouse ES and iPS cells gave various perspectives in understanding the miRNA core regulatory networks regulating pluripotent cells characteristics.
    PLoS ONE 09/2013; 8(9):e73532. DOI:10.1371/journal.pone.0073532 · 3.23 Impact Factor
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