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A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening
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A genome-wide RNAi screen reveals MAP kinase phosphatases as key ERK pathway regulators during embryonic stem cell

Shen-Hsi Yang1, Tuzer Kalkan, Claire Morrisroe

  • 1Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.

Plos Genetics
|December 29, 2012
PubMed

Insights

Mouse embryonic stem cells lose pluripotency via differentiation regulated by ERK and GSK3 pathways. A genome-wide screen identified over 400 genes, highlighting MAP kinase phosphatases as key regulators of cell fate decisions.

Area of Science:

  • Stem cell biology
  • Molecular and cellular signaling

Background:

  • Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are crucial for regenerative medicine.
  • Pluripotency maintenance and differentiation are controlled by intricate transcriptional and signaling networks.

Purpose of the Study:

  • To investigate the differentiation process in mouse ESCs and the roles of ERK MAP kinase and GSK3 signaling pathways.
  • To identify genes involved in pluripotency loss and differentiation onset.

Main Methods:

  • Genome-wide siRNA screen to identify regulatory genes.
  • Functional association analysis of identified genes with ERK and GSK3 pathways.

Main Results:

  • Over 400 genes were identified as involved in pluripotency loss and differentiation.
  • Identified genes are functionally linked to the ERK and/or GSK3 signaling pathways.
  • MAP kinase phosphatases were highlighted as critical regulators of ERK activation kinetics and ESC fate.

Conclusions:

  • ERK and GSK3 signaling pathways are central to ESC differentiation and pluripotency loss.
  • MAP kinase phosphatases play a pivotal role in controlling the timing of ERK activation, thereby influencing early ESC fate decisions.

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