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; Thomas Preiss

doi:10.1038/ncomms6522

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

Nat Commun. 2014 Dec 10:5:5522. doi: 10.1038/ncomms6522.

Authors

Jennifer L Clancy¹, Hardip R Patel², Samer M I Hussein³, Peter D Tonge³, Nicole Cloonan⁴, Andrew J Corso⁵, Mira Li³, Dong-Sung Lee⁶, Jong-Yeon Shin⁷, Justin J L Wong⁸, Charles G Bailey⁸, Marco Benevento⁹, Javier Munoz⁹, Aaron Chuah¹⁰, David Wood⁴, John E J Rasko¹¹, Albert J R Heck⁹, Sean M Grimmond⁴, Ian M Rogers¹², Jeong-Sun Seo¹³, Christine A Wells¹⁴, Mira C Puri¹⁵, Andras Nagy¹⁶, Thomas Preiss¹⁷

Affiliations

¹ Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
² 1] Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia [2] Genome Discovery Unit, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
³ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
⁴ Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
⁵ 1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 [2] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5T 3H7.
⁶ 1] Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, Korea [2] Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea [3] Department of Biochemistry, Seoul National University College of Medicine, Seoul 110-799, Korea.
⁷ 1] Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, Korea [2] Life Science Institute, Macrogen Inc., Seoul 153-781, Korea.
⁸ 1] Gene and Stem Cell Therapy Program, Centenary Institute, Camperdown, New South Wales 2050, Australia [2] Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
⁹ 1] Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands [2] Netherlands Proteomics Centre, Padualaan 8, 3584 CH Utrecht, The Netherlands.
¹⁰ Genome Discovery Unit, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
¹¹ 1] Gene and Stem Cell Therapy Program, Centenary Institute, Camperdown, New South Wales 2050, Australia [2] Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia [3] Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.
¹² 1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 [2] Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada M5T 3H7 [3] Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5T 3H7.
¹³ 1] Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, Korea [2] Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea [3] Department of Biochemistry, Seoul National University College of Medicine, Seoul 110-799, Korea [4] Life Science Institute, Macrogen Inc., Seoul 153-781, Korea.
¹⁴ 1] Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia [2] Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
¹⁵ 1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M5T 3H7.
¹⁶ 1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 [2] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5T 3H7 [3] Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario, Canada M5T 3H7.
¹⁷ 1] Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia [2] Molecular, Structural &Computational Biology Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia.

PMID: 25494340
DOI: 10.1038/ncomms6522

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.