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Nat Commun. 2014 Dec 10;5:5613. doi: 10.1038/ncomms6613.

Proteome adaptation in cell reprogramming proceeds via distinct transcriptional networks.

Author information

1
1] 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, 3584 CH Utrecht, The Netherlands.
2
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5.
3
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.
4
Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
5
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 M5G 1L4 [3] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5T 3H7.

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.

PMID:
25494451
DOI:
10.1038/ncomms6613

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