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Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4
Published on: April 7, 2008
Phosphorylation of Sox2 cooperates in reprogramming to pluripotent stem cells
Chul-Ho Jeong1, Yong-Yeon Cho, Myoung-Ok Kim
1The Hormel Institute, University of Minnesota, Austin, Minnesota 55912, USA.
Stem Cells (Dayton, Ohio)
|October 15, 2010
Summary
Sox2 protein stabilization by Akt phosphorylation enhances its activity, promoting both embryonic stem cell self-renewal and efficient reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). This reveals a key phosphorylation-based regulatory mechanism.
Area of Science:
- Stem cell biology
- Molecular mechanisms of reprogramming
- Epigenetics and gene regulation
Background:
- Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) using reprogramming factors like Oct4, Sox2, Klf4, and c-Myc.
- Sox2, alongside Oct4, is a master regulator of pluripotency in embryonic stem cells (ESCs), but its precise role in self-renewal and reprogramming is not fully understood.
Purpose of the Study:
- To investigate the regulatory mechanisms of Sox2 activity in ESCs and its role in somatic cell reprogramming.
- To explore the potential involvement of post-translational modifications, specifically phosphorylation, in regulating Sox2 function.
Main Methods:
- Investigated the interaction between Akt and Sox2.
- Analyzed the effect of Akt-mediated phosphorylation of Sox2 at Thr118 on its stability and transcriptional activity in ESCs.
- Assessed the impact of Sox2 phosphorylation on the efficiency of induced pluripotent stem cell reprogramming from mouse embryonic fibroblasts.
Main Results:
- Demonstrated direct interaction between Akt and Sox2.
- Showed that Akt phosphorylates Sox2 at Thr118, leading to enhanced Sox2 stabilization and increased transcriptional activity in ESCs.
- Confirmed that phosphorylation of Sox2 significantly improves the efficiency of iPSC generation from mouse embryonic fibroblasts.
Conclusions:
- Sox2 activity is regulated by phosphorylation, with Akt-mediated phosphorylation at Thr118 enhancing its function in ESCs.
- Phosphorylation of Sox2 is a critical event that facilitates efficient somatic cell reprogramming into iPSCs.
- These findings elucidate a novel phosphorylation-based regulatory pathway for Sox2, linking it directly to pluripotency and reprogramming processes.
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