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Cell Stem Cell. 2014 May 1;14(5):606-16. doi: 10.1016/j.stem.2014.02.005. Epub 2014 Mar 13.

Multifaceted regulation of somatic cell reprogramming by mRNA translational control.

Author information

1
The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montréal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montréal, QC H3A 1A3, Canada.
2
Children's Hospital of Eastern Ontario Research Institute and Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
3
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
4
The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montréal, QC H3A 1A3, Canada; Department of Medicine, McGill University Health Center, Montréal, QC H3A 1A3, Canada.
5
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montréal General Hospital, Montréal, QC H3G 1A4, Canada.
6
Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
7
Patrick Wild Centre, Centre for Integrative Physiology, University of Edinburgh, Edinburgh EH8 9XD, UK.
8
The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montréal, QC H3A 1A3, Canada; Department of Human Genetics, McGill University, Montréal, QC H3A 1A3, Canada.
9
The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montréal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montréal, QC H3A 1A3, Canada; Department of Medicine, McGill University Health Center, Montréal, QC H3A 1A3, Canada. Electronic address: xiang-jiao.yang@mcgill.ca.
10
The Rosalind and Morris Goodman Cancer Research Center, McGill University, Montréal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montréal, QC H3A 1A3, Canada; Department of Medicine, McGill University Health Center, Montréal, QC H3A 1A3, Canada. Electronic address: nahum.sonenberg@mcgill.ca.

Abstract

Translational control plays a pivotal role in the regulation of the pluripotency network in embryonic stem cells, but its effect on reprogramming somatic cells to pluripotency has not been explored. Here, we show that eukaryotic translation initiation factor 4E (eIF4E) binding proteins (4E-BPs), which are translational repressors, have a multifaceted effect on the reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs). Loss of 4E-BP expression attenuates the induction of iPSCs at least in part through increased translation of p21, a known inhibitor of somatic cell reprogramming. However, MEFs lacking both p53 and 4E-BPs show greatly enhanced reprogramming resulting from a combination of reduced p21 transcription and enhanced translation of endogenous mRNAs such as Sox2 and Myc and can be reprogrammed through the expression of only exogenous Oct4. Thus, 4E-BPs exert both positive and negative effects on reprogramming, highlighting the key role that translational control plays in regulating this process.

PMID:
24630793
DOI:
10.1016/j.stem.2014.02.005
[Indexed for MEDLINE]
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