Small RNA changes en route to distinct cellular states of induced pluripotency

Jennifer L. Clancy, Hardip R. Patel, Samer M.I. Hussein, Peter D. Tonge, Nicole Cloonan, Andrew J. Corso, Mira Li, Dong Sung Lee, Jong Yeon Shin, Justin J.L. Wong, Charles G. Bailey, Marco Benevento, Javier Munoz, Aaron Chuah, David Wood, John E.J. Rasko, Albert J.R. Heck, Sean M. Grimmond, Ian M. Rogers, Jeong Sun SeoChristine A. Wells, Mira C. Puri, Andras Nagy, Thomas Preiss

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


MicroRNAs (miRNAs) are critical to somatic cell reprogramming into induced pluripotent stem cells (iPSCs), however, exactly how miRNA expression changes support the transition to pluripotency requires further investigation. Here we use a murine secondary reprogramming system to sample cellular trajectories towards iPSCs or a novel pluripotent 'F-class' state and perform small RNA sequencing. We detect sweeping changes in an early and a late wave, revealing that distinct miRNA milieus characterize alternate states of pluripotency. miRNA isoform expression is common but surprisingly varies little between cell states. Referencing other omic data sets generated in parallel, we find that miRNA expression is changed through transcriptional and post-transcriptional mechanisms. miRNA transcription is commonly regulated by dynamic histone modification, while DNA methylation/demethylation consolidates these changes at multiple loci. Importantly, our results suggest that a novel subset of distinctly expressed miRNAs supports pluripotency in the F-class state, substituting for miRNAs that serve such roles in iPSCs.

Original languageEnglish
Article number5522
JournalNature Communications
StatePublished - 2014


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