Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks

Marco Benevento, Peter D. Tonge, Mira C. Puri, Samer M. I. Hussein, Nicole Cloonan, David L. Wood, Sean M. Grimmond, Andras Nagy, Javier Munoz () and Albert J. R. Heck ()
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Marco Benevento: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
Peter D. Tonge: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Mira C. Puri: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Samer M. I. Hussein: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Nicole Cloonan: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
David L. Wood: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
Sean M. Grimmond: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland
Andras Nagy: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Javier Munoz: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University
Albert J. R. Heck: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract The ectopic expression of Oct4, Klf4, c-Myc and Sox2 (OKMS) transcription factors allows reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). The reprogramming process, which involves a complex network of molecular events, is not yet fully characterized. Here we perform a quantitative mass spectrometry-based analysis to probe in-depth dynamic proteome changes during somatic cell reprogramming. Our data reveal defined waves of proteome resetting, with the first wave occurring 48 h after the activation of the reprogramming transgenes and involving specific biological processes linked to the c-Myc transcriptional network. A second wave of proteome reorganization occurs in a later stage of reprogramming, where we characterize the proteome of two distinct pluripotent cellular populations. In addition, the overlay of our proteome resource with parallel generated -omics data is explored to identify post-transcriptionally regulated proteins involved in key steps during reprogramming.

Date: 2014
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DOI: 10.1038/ncomms6613

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