Activation of GSK3b by Sirt2 Is Required for Early Lineage Commitment of Mouse Embryonic Stem Cell

作者：Si, Xiaoxing; Chen, Wen; Guo, Xudong; Chen, Long; Wang, Guiying; Xu, Yanxin; Kang, Jiuhong^*

来源：PLos One, 2013, 8(10): e76699.

DOI：10.1371/journal.pone.0076699

• DIFFERENTIATION
• PLURIPOTENCY
• INHIBITION
• DEACETYLASE
• EXPRESSION
• GENERATION
• SURVIVAL
• GENES
• WNT

Sirt2, a member of the NAD( )-dependent protein deacetylase family, is increasingly recognized as a critical regulator of the cell cycle, cellular necrosis and cytoskeleton organization. However, its role in embryonic stem cells (ESCs) remains unclear. Here we demonstrate that Sirt2 is up-regulated during RA (retinoic acid)-induced and embryoid body (EB) differentiation of mouse ESCs. Using lentivirus-mediated shRNA methods, we found that knockdown of Sirt2 compromises the differentiation of mouse ESCs into ectoderm while promoting mesoderm and endoderm differentiation. Knockdown of Sirt2 expression also leads to the activation of GSK3 beta through decreased phosphorylation of the serine at position 9 (Ser9) but not tyrosine at position 216 (Tyr216). Moreover, the constitutive activation of GSK3 beta during EB differentiation mimics the effect of Sirt2 knockdown, while down-regulation of GSK3 beta rescues the effect of Sirt2 knockdown on differentiation. In contrast to the effect on lineage differentiation, Sirt2 knockdown and GSK3 beta up-regulation do not change the self-renewal state of mouse ESCs. Overall, our report reveals a new function for Sirt2 in regulating the proper lineage commitment of mouse ESCs.

• 出版日期2013-10-18
• 单位同济大学