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

Gennaro Gambardella, Annamaria Carissimo, Amy Chen, Luisa Cutillo, Tomasz J. Nowakowski, Diego di Bernardo () and Robert Blelloch ()
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Gennaro Gambardella: Telethon Institute of Genetics and Medicine
Annamaria Carissimo: Telethon Institute of Genetics and Medicine
Amy Chen: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California
Luisa Cutillo: Telethon Institute of Genetics and Medicine
Tomasz J. Nowakowski: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California
Diego di Bernardo: Telethon Institute of Genetics and Medicine
Robert Blelloch: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms14126

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