The functions of microRNAs in pluripotency and reprogramming

1] Department of Chemical Physiology, The Scripps Research Institute and the Center for Regenerative Medicine, La Jolla, California 92037, USA [2].
Nature Cell Biology (Impact Factor: 19.68). 11/2012; 14(11):1114-21. DOI: 10.1038/ncb2613
Source: PubMed


Pluripotent stem cells (PSCs) express a distinctive set of microRNAs (miRNAs). Many of these miRNAs have similar targeting sequences and are predicted to regulate downstream targets cooperatively. These enriched miRNAs are involved in the regulation of the unique PSC cell cycle, and there is increasing evidence that they also influence other important characteristics of PSCs, including their morphology, epigenetic profile and resistance to apoptosis. Detailed studies of miRNAs and their targets in PSCs should help to parse the regulatory networks that underlie developmental processes and cellular reprogramming.

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Available from: Jeanne F Loring, Oct 10, 2015
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    • "In fact, although the proportion of miRNAs was also high in spermatogonia cells, we observed a decrease in miRNA reads with respect to PGC. This suggests a correlation between abundance of miRNA and cell self-renewal processes and pluripotency (Leonardo et al. 2012; Choi et al. 2013). "
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    ABSTRACT: The small noncoding RNAs (sncRNAs) are considered as post-transcriptional key regulators of male germ cell development. In addition to microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), other sncRNAs generated from small nucleolar RNAs (snoRNAs), tRNAs, or rRNAs processing may also play important regulatory roles in spermatogenesis. By next-generation sequencing (NGS), we characterized the sncRNA populations detected at three milestone stages in male germ differentiation: primordial germ cells (PGCs), pubertal spermatogonia cells, and mature spermatozoa. To assess their potential transmission through the spermatozoa during fertilization, the sncRNAs of mouse oocytes and zygotes were also analyzed. Both, microRNAs and snoRNA-derived small RNAs are abundantly expressed in PGCs but transiently replaced by piRNAs in spermatozoa and endo-siRNAs in oocytes and zygotes. Exhaustive analysis of miRNA sequence variants also shows an increment of noncanonical microRNA forms along male germ cell differentiation. RNAs-derived from tRNAs and rRNAs interacting with PIWI proteins are not generated by the ping-pong pathway and could be a source of primary piRNAs. Moreover, our results strongly suggest that the small RNAs-derived from tRNAs and rRNAs are interacting with PIWI proteins, and specifically with MILI. Finally, computational analysis revealed their potential involvement in post-transcriptional regulation of mRNA transcripts suggesting functional convergence among different small RNA classes in germ cells and zygotes. © 2015 García-López et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
    RNA 03/2015; 21(5). DOI:10.1261/rna.048215.114 · 4.94 Impact Factor
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    • "These genes have been clubbed together in a general class popularly known as noncoding RNAs (ncRNA). Many members of the ncRNA class such as microRNAs (miRNAs) have been extensively studied for their regulatory roles in a variety of cellular processes [Holley and Topkara, 2011; Leonardo et al., 2012; Mo, 2012] and disease mechanisms [Amiel et al., 2012]. Others of the class, such as snoRNAs have been explored for their roles in base modifications [Askarian-Amiri et al., 2011; Holley and Topkara, 2011; Liao et al., 2010]. "
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    ABSTRACT: Non-protein coding RNAs have increasingly been shown to be an important class of regulatory RNAs having significant roles in regulation of gene expression. The long non-coding RNA gene family presently constitutes a large number of noncoding RNA loci almost equalling the number of protein-coding genes. Nevertheless the biological roles and mechanisms of majority of long noncoding RNAs are poorly understood, with exceptions of a very few well studied candidates. The availability of genome-scale variation datasets, and increasing number of variant loci from genome-wide association studies falling in lncRNA loci have motivated us to understand the patterns of genomic variations in lncRNA loci, their potential functional correlates and selection in populations. In the present study, we have performed a comprehensive analysis of genomic variations in lncRNA loci. We analysed for patterns and distributions of genomic variations with respect to potential functional domains in lncRNAs. Analysis reveals a distinct distribution of variations in sub-classes of long noncoding RNAs and in potential functional domains of lncRNAs. We further examined signals of selections and allele frequencies of these prioritised set of lncRNAs. To the best of our knowledge this is the first and comprehensive large-scale analysis of genetic variations in long noncoding RNAs. This article is protected by copyright. All rights reserved.
    Human Mutation 02/2014; 35(2). DOI:10.1002/humu.22472 · 5.14 Impact Factor
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    • "Their profiles unambiguously distinguish cell types, including embryonic stem cells [13,14], a vast variety of precursor cells, terminally differentiated cells, and tumor types, even among closely related cancers [15]. miRNAs play important functional roles in stem cells, including the regulation of pluripotency, self-renewal and reprogramming of somatic cells (reviewed in [16]). "
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    ABSTRACT: MicroRNAs often operate in feedback loops with transcription factors and represent a key mechanism for fine-tuning gene expression. In transcription factor-induced reprogramming, miRNAs play a critical role; however, detailed analyses of miRNA expression changes during reprogramming at the level of deep sequencing have not been previously reported. We use four factor reprogramming to induce pluripotent stem cells from mouse fibroblasts and isolate FACS-sorted Thy1- and SSEA1+ intermediates and Oct4-GFP+ iPSCs. Small RNAs from these cells, and two partial-iPSC lines, another iPS line, and mES cells were deep sequenced. A comprehensive resetting of the miRNA profile occurs during reprogramming; however, analysis of miRNA co-expression patterns yields only a few patterns of change. Dlk1-Dio3 region miRNAs dominate the large pool of miRNAs experiencing small but significant fold changes early in reprogramming. Overexpression of Dlk1-Dio3 miRNAs early in reprogramming reduces reprogramming efficiency, suggesting the observed downregulation of these miRNAs may contribute to reprogramming. As reprogramming progresses, fewer miRNAs show changes in expression, but those changes are generally of greater magnitude. The broad resetting of the miRNA profile during reprogramming that we observe is due to small changes in gene expression in many miRNAs early in the process, and large changes in only a few miRNAs late in reprogramming. This corresponds with a previously observed transition from a stochastic to a more deterministic signal.
    Genome biology 12/2013; 14(12):R149. DOI:10.1186/gb-2013-14-12-r149 · 10.81 Impact Factor
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