A genome-wide RNAi screen reveals MAP kinase phosphatases as key ERK pathway regulators during embryonic stem cell differentiation

Embryonic stem cells and induced pluripotent stem cells represent potentially important therapeutic agents in regenerative medicine. Complex interlinked transcriptional and signaling networks control the fate of these cells towards maintenance of pluripotency or differentiation. In this study we hav...

Full description

Saved in:
Bibliographic Details
Published in:PLoS genetics 2012-12, Vol.8 (12), p.e1003112-e1003112
Main Authors: Yang, Shen-Hsi, Kalkan, Tuzer, Morrisroe, Claire, Smith, Austin, Sharrocks, Andrew D
Format: Article
Language:English
Subjects:
Animals
Biology
Cell Differentiation
Cytogenetics
Embryonic stem cells
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Genetic aspects
Genetic engineering
Genomes
Genomics
Health aspects
Kinases
MAP Kinase Signaling System - genetics
Mice
Mitogen-activated protein kinases
Mitogen-Activated Protein Kinases - genetics
Mitogen-Activated Protein Kinases - metabolism
Phosphoric Monoester Hydrolases - genetics
Phosphoric Monoester Hydrolases - metabolism
Physiological aspects
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
Proteins
RNA, Small Interfering - genetics
Signal Transduction - genetics
Stem cells
Transplants & implants
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Embryonic stem cells and induced pluripotent stem cells represent potentially important therapeutic agents in regenerative medicine. Complex interlinked transcriptional and signaling networks control the fate of these cells towards maintenance of pluripotency or differentiation. In this study we have focused on how mouse embryonic stem cells begin to differentiate and lose pluripotency and, in particular, the role that the ERK MAP kinase and GSK3 signaling pathways play in this process. Through a genome-wide siRNA screen we have identified more than 400 genes involved in loss of pluripotency and promoting the onset of differentiation. These genes were functionally associated with the ERK and/or GSK3 pathways, providing an important resource for studying the roles of these pathways in controlling escape from the pluripotent ground state. More detailed analysis identified MAP kinase phosphatases as a focal point of regulation and demonstrated an important role for these enzymes in controlling ERK activation kinetics and subsequently determining early embryonic stem cell fate decisions.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1003112