刘德培课题组在《Stem Cells》 杂志发表研究论文“Sox2 Deacetylation by Sirt1 Is Involved in Mouse Somatic Reprogramming （2015）”。

体细胞可以被特定因子包括Oct4, Sox2, Klf4, and c-Myc重编程为干细胞，这其中Oct4，Sox2对于重编程具有重要作用。Sirt1是NAD+依赖的去乙酰酶家族的成员，本研究探讨其对于重编程的作用。中国医学科学院基础医学研究所，“医学分子生物学国家重点实验室”的刘德培课题组发现体细胞在向干细胞的重编程中需要Sirt1对于Sox2的的去乙酰化。Sox2的低乙酰化程度显著提高重编程效率，Sirt1缺失的的小鼠胚胎成纤维细胞中，Sox2不能维持低乙酰化，重编程效率降低，而Sirt1的过表达能补救这一缺陷。Sox2的去乙酰化是以Oct4介导的方式进行的。

      【摘要】：Mouse somatic cells can be reprogrammed into induced pluripotent stem cells by defined factors known to regulate pluripotency, including Oct4, Sox2, Klf4, and c-Myc. Together with Oct4, Sox2 plays a major role as a master endogenous pluripotent genes trigger in reprogramming. It has been reported that Sirtuin 1 (Sirt1), a member of the Sirtuin family of NAD(+) -dependent protein deacetylases, is involved in embryonic stem cell antioxidation, differentiation, and individual development. However, as a deacetylation enzyme, whether Sirt1 influences reprogramming through its post-translational modification function remains unknown. In this study, we provide evidence that deacetylation of Sox2 by Sirt1 is required for reprogramming. We found that a low level of Sox2 acetylation could significantly increase reprogramming efficiency. Furthermore, we found that Sox2 can be deacetylated by Sirt1 in an Oct4-mediated manner. Compared with wild-type cells, Sirt1-null mouse embryonic fibroblasts exhibit decreased reprogramming efficiency, and overexpression of Sirt1 rescues this defect. In addition, Sirt1 functions in the regulation of reprogramming through deacetylating Sox2. Taken together, we have identified a new regulatory role of Sirt1 in reprogramming and provided a link between deacetylation events and somatic cell reprogramming. Stem Cells 2015;33:2135-2147.

      相关结果已发表于《Stem Cells》 杂志（2015，2015 Jul;33(7):2135-47. doi: 10.1002/stem.2012. Epub 2015 May 4.），其作者为刘德培课题组博士研究生Mu WL, Wang YJ, Xu P，重点室刘德培研究员是本文的通讯作者。该研究工作得到了以下基金的支持：National Natural Science Foundation of China (nos. 31271227, 30121091, and 81161120551), the National Basic Research Program (nos. 2011CB503902 and 2011CB965203)。