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 Seo, Christine A. Wells, Mira C. Puri, Andras Nagy and Thomas Preiss ()
Additional contact information
Jennifer L. Clancy: The John Curtin School of Medical Research, The Australian National University
Hardip R. Patel: The John Curtin School of Medical Research, The Australian National University
Samer M. I. Hussein: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Peter D. Tonge: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Nicole Cloonan: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
Andrew J. Corso: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Mira Li: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Dong-Sung Lee: Genomic Medicine Institute, Medical Research Center, Seoul National University
Jong-Yeon Shin: Genomic Medicine Institute, Medical Research Center, Seoul National University
Justin J. L. Wong: Gene and Stem Cell Therapy Program, Centenary Institute
Charles G. Bailey: Gene and Stem Cell Therapy Program, Centenary Institute
Marco Benevento: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
Javier Munoz: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
Aaron Chuah: Genome Discovery Unit, The John Curtin School of Medical Research, The Australian National University
David Wood: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
John E. J. Rasko: Gene and Stem Cell Therapy Program, Centenary Institute
Albert J. R. Heck: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
Sean M. Grimmond: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
Ian M. Rogers: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Jeong-Sun Seo: Genomic Medicine Institute, Medical Research Center, Seoul National University
Christine A. Wells: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland
Mira C. Puri: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Andras Nagy: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Thomas Preiss: The John Curtin School of Medical Research, The Australian National University

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms6522

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