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, Albert J.R. Heck

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Article number5613
Number of pages11
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 10 Dec 2014
Externally publishedYes

Keywords

  • pluripotent stem cells
  • proteomics
  • reprogramming
  • transcription

Cite this