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Nat Commun. 2017 Jan 19;8:14126. doi: 10.1038/ncomms14126.

The impact of microRNAs on transcriptional heterogeneity and gene co-expression across single embryonic stem cells.

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Telethon Institute of Genetics and Medicine, Pozzuoli, 80078 Naples, Italy.
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USA.
Department of Urology, University of California, San Francisco, San Francisco, California 94143, USA.
Department of Chemical, Materials and Industrial Engineering, University of Naples 'Federico II', 80125 Naples, Italy.


MicroRNAs act posttranscriptionally to suppress multiple target genes within a cell population. To what extent this multi-target suppression occurs in individual cells and how it impacts transcriptional heterogeneity and gene co-expression remains unknown. Here we used single-cell sequencing combined with introduction of individual microRNAs. miR-294 and let-7c were introduced into otherwise microRNA-deficient Dgcr8 knockout mouse embryonic stem cells. Both microRNAs induce suppression and correlated expression of their respective gene targets. The two microRNAs had opposing effects on transcriptional heterogeneity within the cell population, with let-7c increasing and miR-294 decreasing the heterogeneity between cells. Furthermore, let-7c promotes, whereas miR-294 suppresses, the phasing of cell cycle genes. These results show at the individual cell level how a microRNA simultaneously has impacts on its many targets and how that in turn can influence a population of cells. The findings have important implications in the understanding of how microRNAs influence the co-expression of genes and pathways, and thus ultimately cell fate.

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