Evidence map›Paper›PMID 25503233›Full record

ArticleNature2014

Genome-wide characterization of the routes to pluripotency.

Samer M I Hussein, Mira C Puri, Peter D Tonge, Marco Benevento, Andrew J Corso, Jennifer L Clancy, Rowland Mosbergen, Mira Li, Dong-Sung Lee, Nicole Cloonan and 22 more

Erratum issuedAbstract read
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In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 124 papers.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

124 citing papers in PubMed.

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  15. Article
  16. Highly efficient reprogrammable mouse lines with integrated reporters to track the route to pluripotency.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  17. Article
  18. Article
  19. Article
  20. The Defects of Epigenetic Reprogramming in Dox-Dependent Porcine-iPSCs.International journal of molecular sciences · 2022
    Article

64 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors.

Samer M I HusseinLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Mira C Puri1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5T 3H7, Canada.
Peter D TongeLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Marco Benevento1] Biomolecular Mass Spectrometry and Proteomics, 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, 3584CH Utrecht, The Netherlands.
Andrew J Corso1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada [2] Institute of Medical Science, University of Toronto, Toronto, Ontario M5T 3H7, Canada.
Jennifer L ClancyGenome Biology Department, The John Curtin School of Medical Research, The Australian National University, Acton (Canberra), ACT 2601, Australia.
Rowland MosbergenAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.
Mira LiLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
Dong-Sung Lee1] Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, South Korea [2] Department of Biomedical Sciences and Biochemistry, Seoul National University College of Medicine, Seoul 110-799, South Korea.
Nicole CloonanQueensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
David L A WoodQueensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
Javier Munoz1] Biomolecular Mass Spectrometry and Proteomics, 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, 3584CH Utrecht, The Netherlands.
Robert MiddletonGene and Stem Cell Therapy Program and Bioinformatics Lab, Centenary Institute, Camperdown 2050, NSW, Australia &Sydney Medical School, 31 University of Sydney 2006, New South Wales, Australia.
Othmar KornAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia.
Hardip R Patel1] Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Acton (Canberra), ACT 2601, Australia [2] Genome Discovery Unit, The John Curtin School of Medical Research, The Australian National University, Acton (Canberra) 2601, ACT, Australia.
Carl A White1] Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto M5S-3G9, Canada [2] The Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, Toronto M5S 3E1, Canada.
Jong-Yeon Shin1] Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, South Korea [2] Life Science Institute, Macrogen Inc., Seoul 153-781, South Korea.
Maely E GauthierQueensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
Kim-Anh Lê CaoQueensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
Jong-Il Kim1] Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, South Korea [2] Department of Biomedical Sciences and Biochemistry, Seoul National University College of Medicine, Seoul 110-799, South Korea.
Jessica C MarDepartment of Systems &Computational Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA.
Nika ShakibaInstitute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto M5S-3G9, Canada.
William RitchieGene and Stem Cell Therapy Program and Bioinformatics Lab, Centenary Institute, Camperdown 2050, NSW, Australia &Sydney Medical School, 31 University of Sydney 2006, New South Wales, Australia.
John E J Rasko1] Gene and Stem Cell Therapy Program and Bioinformatics Lab, Centenary Institute, Camperdown 2050, NSW, Australia &Sydney Medical School, 31 University of Sydney 2006, New South Wales, Australia [2] Cell and Molecular Therapies, Royal Prince Alfred Hospital, Camperdown 2050, New South Wales, Australia.
Sean M GrimmondQueensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
Peter W Zandstra1] Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto M5S-3G9, Canada [2] The Donnelly Centre for Cellular and Biomolecular Research (CCBR), University of Toronto, Toronto M5S 3E1, Canada.
Christine A Wells1] Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia [2] College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
Thomas Preiss1] Genome Biology Department, The John Curtin School of Medical Research, The Australian National University, Acton (Canberra), ACT 2601, Australia [2] Victor Chang Cardiac Research Institute, Darlinghurst (Sydney), New South Wales 2010, Australia.
Jeong-Sun Seo1] Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul 110-799, South Korea [2] Department of Biomedical Sciences and Biochemistry, Seoul National University College of Medicine, Seoul 110-799, South Korea [3] Life Science Institute, Macrogen Inc., Seoul 153-781, South Korea.
Albert J R Heck1] Biomolecular Mass Spectrometry and Proteomics, 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, 3584CH Utrecht, The Netherlands.
Ian M Rogers1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada [2] Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario M5S 1E2, Canada.
Andras Nagy1] Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada [2] Institute of Medical Science, University of Toronto, Toronto, Ontario M5T 3H7, Canada [3] Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Ontario M5S 1E2, Canada.

Funding

Canadian Institutes of Health Research MOP102575
6 · The paper itself

Abstract

Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and -independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org.

Indexed as

AnimalsCellular ReprogrammingChromatinChromatin Assembly and DisassemblyDNA MethylationEmbryonic Stem CellsEpistasis, GeneticFibroblastsGenomeHistonesInduced Pluripotent Stem CellsInternetMiceProteomeProteomicsRNA, Long NoncodingChromatinHistonesProteomeRNA, Long NoncodingTranscription Factors

Identifiers

PMID25503233

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.