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Embryonic stem cell–specific microRNAs promote induced pluripotency

Abstract

This report demonstrates that introduction of microRNAs (miRNAs) specific to embryonic stem cells enhances the production of mouse induced pluripotent stem (iPS) cells. The miRNAs miR-291-3p, miR-294 and miR-295 increase the efficiency of reprogramming by Oct4, Sox2 and Klf4, but not by these factors plus cMyc. cMyc binds the promoter of the miRNAs, suggesting that they are downstream effectors of cMyc during reprogramming. However, unlike cMyc, the miRNAs induce a homogeneous population of iPS cell colonies.

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Figure 1: The ESCC miRNAs promote three-factor- but not four-factor-induced pluripotency.
Figure 2: Characterization of the relationship between cMyc and miR-294.

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Acknowledgements

We would like to thank Deepa Subramanyam, Yangming Wang and Kathryn Blaschke for technical advice and experimental suggestions, as well as Marco Conti, Diana Laird and members of the Blelloch Laboratory for critical reading of the manuscript. This work was supported by funds to R.B. from California Institute for Regenerative Medicine (RS1-00161) and the National Institutes of Health (NIH) (K08 NS48118 and R01 NS057221). R.L.J. is supported by a National Science Foundation Graduate Research Fellowship. M.V. is supported by an NIH training fellowship (F32NS058042). R.B. is a Pew Scholar.

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R.L.J. performed all experiments. J.E.B. analyzed ChIP-seq data. M.V. analyzed the chimeras. R.L.J. and R.B. designed all experiments, analyzed data and wrote the manuscript.

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Correspondence to Robert Blelloch.

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Supplementary Figures 1–7, Supplementary Tables 1,2 and Supplementary Methods (PDF 969 kb)

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Judson, R., Babiarz, J., Venere, M. et al. Embryonic stem cell–specific microRNAs promote induced pluripotency. Nat Biotechnol 27, 459–461 (2009). https://doi.org/10.1038/nbt.1535

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