Investigating Functional Consequences of miRNA Expression During Somatic Cell Reprogramming (Pages: 0-0)


Mohammadsharif Tabebordbar *, Stuart Levine , Ghasem Hosseini Salekdeh , Laurie A. Boyer ,

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The recent generation of induced pluripotent stem cells (iPSCs) from somatic cells provides an invaluable resource for drug or toxicology screening, medical research, and patient-specific cell therapy. However, the mechanisms underlying reprogramming still remain largely unknown. Reprogramming is a gradual process in which a small fraction of transduced cells undergo global changes in gene expression profiles, histone modification and DNA methylation patterns, while the majority of cells do not fully reprogram and remain in a partially reprogrammed state. MicroRNAs which are ~22 nucleotide single-stranded RNA molecules, have emerged as important regulators of gene expression and also appear to converge with the core regulatory circuitry controlling self-renewal and pluripotency in ES cells. To investigate the role of miRNAs in the process of reprogramming, we defined the set of miRNAs expressed during different stages of mouse embryonic fibroblast (MEF) reprogramming by deep sequencing. We found a subset of miRNAs that are differentially expressed in MEF, intermediate cells and iPSCs. Significant differences in the expression level of some miRNAs in different stages of reprogramming suggest that these molecules, along with other regulators of gene expression, might have a role in de-differentioan of somatic cells. We are currently testing the role of a selective set of miRNAs in reprogramming by a variety of methods.