title: Small RNA changes en route to distinct cellular states of induced pluripotency.
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.
authors.affiliation: Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Clancy
authors.affiliation: 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.
authors.forename: Hardip R
authors.initials: HR
authors.lastname: Patel
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Samer M I
authors.initials: SM
authors.lastname: Hussein
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Tonge
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Cloonan
authors.affiliation: 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.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Corso
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
authors.forename: Mira
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: 1] Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, Korea [2] Life Science Institute, Macrogen Inc., Seoul 153-781, Korea.
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Shin
authors.affiliation: 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.
authors.forename: Justin J L
authors.initials: JJ
authors.lastname: Wong
authors.affiliation: 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.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Bailey
authors.affiliation: 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.
authors.forename: Marco
authors.initials: M
authors.lastname: Benevento
authors.affiliation: 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.
authors.forename: Javier
authors.initials: J
authors.lastname: Munoz
authors.affiliation: Genome Discovery Unit, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Aaron
authors.initials: A
authors.lastname: Chuah
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Wood
authors.affiliation: 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.
authors.forename: John E J
authors.initials: JE
authors.lastname: Rasko
authors.affiliation: 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.
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.affiliation: 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.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Rogers
authors.affiliation: 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.
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
authors.affiliation: 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.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Wells
authors.affiliation: 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.
authors.forename: Mira C
authors.initials: MC
authors.lastname: Puri
authors.affiliation: 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.
authors.forename: Andras
authors.initials: A
authors.lastname: Nagy
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Preiss