Sox2 Deacetylation by Sirt1 Is Involved in Mouse Somatic Reprogramming

Area of Science:

• Cell biology
• Stem cell research
• Epigenetics

Background:

• Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) is mediated by key transcription factors like Oct4 and Sox2.
• Sirtuin 1 (Sirt1), an NAD(+)-dependent deacetylase, is implicated in embryonic stem cell functions but its role in reprogramming is unclear.
• The post-translational modification function of Sirt1 in reprogramming requires investigation.

Purpose of the Study:

• To investigate the role of Sirt1 in the reprogramming of mouse somatic cells into iPSCs.
• To determine if Sirt1 influences reprogramming through the post-translational modification of key reprogramming factors.
• To elucidate the mechanism by which Sirt1 regulates reprogramming efficiency.

Main Methods:

• Assessing reprogramming efficiency in Sirt1-null mouse embryonic fibroblasts (MEFs) compared to wild-type cells.
• Evaluating the effect of Sirt1 overexpression on reprogramming efficiency.
• Investigating the interaction and deacetylation of Sox2 by Sirt1, mediated by Oct4.

Main Results:

• Sirt1-null MEFs exhibited significantly decreased reprogramming efficiency.
• Overexpression of Sirt1 rescued the reprogramming defect in Sirt1-null cells.
• Sirt1 deacetylates Sox2 in an Oct4-mediated manner, and reduced Sox2 acetylation enhances reprogramming efficiency.

Conclusions:

• Sirt1-mediated deacetylation of Sox2 is essential for efficient somatic cell reprogramming.
• This study identifies a novel regulatory mechanism for Sirt1 in reprogramming via Sox2 post-translational modification.
• The findings establish a direct link between deacetylation events and the process of somatic cell reprogramming.