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

Author

Listed:
  • 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
    Genome Discovery Unit, 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
    Present address: Genomic Biology Laboratory, Genetics & Computational Biology Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia)

  • Andrew J. Corso

    (Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
    Institute of Medical Science, University of Toronto)

  • Mira Li

    (Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital)

  • Dong-Sung Lee

    (Genomic Medicine Institute, Medical Research Center, Seoul National University
    Seoul National University College of Medicine
    Seoul National University College of Medicine)

  • Jong-Yeon Shin

    (Genomic Medicine Institute, Medical Research Center, Seoul National University
    Life Science Institute, Macrogen Inc.)

  • Justin J. L. Wong

    (Gene and Stem Cell Therapy Program, Centenary Institute
    Sydney Medical School, University of Sydney)

  • Charles G. Bailey

    (Gene and Stem Cell Therapy Program, Centenary Institute
    Sydney Medical School, University of Sydney)

  • Marco Benevento

    (Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
    Netherlands Proteomics Centre)

  • Javier Munoz

    (Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
    Netherlands Proteomics Centre
    Present address: ISCIII-ProteoRed Proteomics Unit, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain)

  • 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
    Sydney Medical School, University of Sydney
    Cell and Molecular Therapies, Royal Prince Alfred Hospital)

  • Albert J. R. Heck

    (Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
    Netherlands Proteomics Centre)

  • 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
    University of Toronto
    University of Toronto)

  • Jeong-Sun Seo

    (Genomic Medicine Institute, Medical Research Center, Seoul National University
    Seoul National University College of Medicine
    Seoul National University College of Medicine
    Life Science Institute, Macrogen Inc.)

  • Christine A. Wells

    (Australian Institute for Bioengineering and Nanotechnology, The University of Queensland
    Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow)

  • Mira C. Puri

    (Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
    University of Toronto)

  • Andras Nagy

    (Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
    Institute of Medical Science, University of Toronto
    University of Toronto)

  • Thomas Preiss

    (The John Curtin School of Medical Research, The Australian National University
    Molecular, Victor Chang Cardiac Research Institute)

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.

Suggested Citation

  • 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 & Marc, 2014. "Small RNA changes en route to distinct cellular states of induced pluripotency," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6522
    DOI: 10.1038/ncomms6522
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