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; David L. A. Wood; Javier Munoz; Robert Middleton; Othmar Korn; Hardip R. Patel; Carl A. White; Jong-Yeon Shin; Maely E. Gauthier; Kim-Anh Le Cao; Jong-Il Kim; Jessica C. Mar; Nika Shakiba; William Ritchie; John E. J. Rasko; Sean M. Grimmond; Peter W. Zandstra; Christine A. Wells; Thomas Preiss; Jeong-Sun Seo; Albert J. R. Heck; Ian M. Rogers; Andras Nagy

doi:10.1038/nature14046

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Genome-wide characterization of the routes to pluripotency

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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, …

Nature (London), Vol.516(7530), pp.198-206

11/12/2014

DOI: https://doi.org/10.1038/nature14046

PMID: 25503233

Résumé

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

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.

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Titre: Genome-wide characterization of the routes to pluripotency
Créateurs - sans rôle: Samer M. I. Hussein - Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
Mira C. Puri - Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
Peter D. Tonge - Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
Marco Benevento - Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands
Andrew J. Corso - Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
Jennifer L. Clancy - Australian Natl Univ, John Curtin Sch Med Res, Genome Biol Dept, Canberra, ACT 2601, Australia
Rowland Mosbergen - Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia
Mira Li - Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
Dong-Sung Lee - Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul 110799, South Korea
Nicole Cloonan - Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, St Lucia, Qld 4072, Australia
David L. A. Wood - Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, St Lucia, Qld 4072, Australia
Javier Munoz - Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands
Robert Middleton - Centenary Inst, Gene & Stem Cell Therapy Program, Camperdown, NSW 2050, Australia
Othmar Korn - Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld 4072, Australia
Hardip R. Patel - Australian Natl Univ, John Curtin Sch Med Res, Genome Biol Dept, Canberra, ACT 2601, Australia
Carl A. White - Univ Toronto, Inst Biomat & Biomed Engn IBBME, Toronto, ON M5S 3G9, Canada
Jong-Yeon Shin - Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul 110799, South Korea
Maely E. Gauthier - Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, St Lucia, Qld 4072, Australia
Kim-Anh Le Cao - Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, St Lucia, Qld 4072, Australia
Jong-Il Kim - Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul 110799, South Korea
Jessica C. Mar - Yeshiva Univ, Albert Einstein Coll Med, Dept Syst & Computat Biol, Bronx, NY 10461 USA
Nika Shakiba - Univ Toronto, Inst Biomat & Biomed Engn IBBME, Toronto, ON M5S 3G9, Canada
William Ritchie - Centenary Inst, Gene & Stem Cell Therapy Program, Camperdown, NSW 2050, Australia
John E. J. Rasko - Centenary Institute
Sean M. Grimmond - Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Genom, St Lucia, Qld 4072, Australia
Peter W. Zandstra - Univ Toronto, Inst Biomat & Biomed Engn IBBME, Toronto, ON M5S 3G9, Canada
Christine A. Wells - The University of Queensland
Thomas Preiss - Australian Natl Univ, John Curtin Sch Med Res, Genome Biol Dept, Canberra, ACT 2601, Australia
Jeong-Sun Seo - Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul 110799, South Korea
Albert J. R. Heck - Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands
Ian M. Rogers - Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
Andras Nagy - Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
Détails de publication: Nature (London), Vol.516(7530), pp.198-206
Éditeur: Springer Nature
Nombre de pages: 26
Note de subvention: MGR03-11; MGR03-12 / Macrogen Inc. 1024852 / National Health and Medical Research Council of Australia; National Health & Medical Research Council (NHMRC) of Australia Netherlands Proteomics Centre DP1300101928; SR110001002 / Australian Research Council GL2-01-028 / Ontario Research Fund Global Leadership Round in Genomics and Life Sciences grants 0411-20100074 / SNUCM Research Fund 262067 / European Community's Seventh Framework Programme (FP7) by the PRIME-XS project 9/5254 (TR3) / Canadian stem cell network Cancer Council of NSW; Cancer Council New South Wales 571156; 1061906 / National Health & Medical Research Council; National Health & Medical Research Council (NHMRC) of Australia
Identifiants: 99139797109311
Unité académique: Institut de Génétique Humaine - IGH
Langue: English
Type de ressource: Journal article