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Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency

Hansson, Jenny LU ; Rafiee, Mahmoud Reza; Reiland, Sonja; Polo, Jose M; Gehring, Julian; Okawa, Satoshi; Huber, Wolfgang; Hochedlinger, Konrad and Krijgsveld, Jeroen (2012) In Cell Reports 2(6). p.92-1579
Abstract

Generation of induced pluripotent stem cells (iPSCs) is a process whose mechanistic underpinnings are only beginning to emerge. Here, we applied in-depth quantitative proteomics to monitor proteome changes during the course of reprogramming of fibroblasts to iPSCs. We uncover a two-step resetting of the proteome during the first and last 3 days of reprogramming, with multiple functionally related proteins changing in expression in a highly coordinated fashion. This comprised several biological processes, including changes in the stoichiometry of electron transport-chain complexes, repressed vesicle-mediated transport during the intermediate stage, and an EMT-like process in the late phase. In addition, we demonstrate that the... (More)

Generation of induced pluripotent stem cells (iPSCs) is a process whose mechanistic underpinnings are only beginning to emerge. Here, we applied in-depth quantitative proteomics to monitor proteome changes during the course of reprogramming of fibroblasts to iPSCs. We uncover a two-step resetting of the proteome during the first and last 3 days of reprogramming, with multiple functionally related proteins changing in expression in a highly coordinated fashion. This comprised several biological processes, including changes in the stoichiometry of electron transport-chain complexes, repressed vesicle-mediated transport during the intermediate stage, and an EMT-like process in the late phase. In addition, we demonstrate that the nucleoporin Nup210 is essential for reprogramming by its permitting of rapid cellular proliferation and subsequent progression through MET. Along with the identification of proteins expressed in a stage-specific manner, this study provides a rich resource toward an enhanced mechanistic understanding of cellular reprogramming.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Cell Line, Cell Proliferation, Induced Pluripotent Stem Cells, Mice, Nuclear Pore Complex Proteins, Proteome
in
Cell Reports
volume
2
issue
6
pages
14 pages
publisher
Cell Press
external identifiers
  • Scopus:84871683601
ISSN
2211-1247
DOI
10.1016/j.celrep.2012.10.014
language
English
LU publication?
no
id
c90a70bd-7e4d-4162-95b0-8655a3cbbb74
date added to LUP
2016-08-25 09:49:26
date last changed
2017-02-19 04:40:17
@article{c90a70bd-7e4d-4162-95b0-8655a3cbbb74,
  abstract     = {<p>Generation of induced pluripotent stem cells (iPSCs) is a process whose mechanistic underpinnings are only beginning to emerge. Here, we applied in-depth quantitative proteomics to monitor proteome changes during the course of reprogramming of fibroblasts to iPSCs. We uncover a two-step resetting of the proteome during the first and last 3 days of reprogramming, with multiple functionally related proteins changing in expression in a highly coordinated fashion. This comprised several biological processes, including changes in the stoichiometry of electron transport-chain complexes, repressed vesicle-mediated transport during the intermediate stage, and an EMT-like process in the late phase. In addition, we demonstrate that the nucleoporin Nup210 is essential for reprogramming by its permitting of rapid cellular proliferation and subsequent progression through MET. Along with the identification of proteins expressed in a stage-specific manner, this study provides a rich resource toward an enhanced mechanistic understanding of cellular reprogramming.</p>},
  author       = {Hansson, Jenny and Rafiee, Mahmoud Reza and Reiland, Sonja and Polo, Jose M and Gehring, Julian and Okawa, Satoshi and Huber, Wolfgang and Hochedlinger, Konrad and Krijgsveld, Jeroen},
  issn         = {2211-1247},
  keyword      = {Animals,Cell Line,Cell Proliferation,Induced Pluripotent Stem Cells,Mice,Nuclear Pore Complex Proteins,Proteome},
  language     = {eng},
  month        = {12},
  number       = {6},
  pages        = {92--1579},
  publisher    = {Cell Press},
  series       = {Cell Reports},
  title        = {Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency},
  url          = {http://dx.doi.org/10.1016/j.celrep.2012.10.014},
  volume       = {2},
  year         = {2012},
}