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Stem Cell Res Ther. 2019 Jan 10;10(1):9. doi: 10.1186/s13287-018-1109-5.

Sirt6 regulates efficiency of mouse somatic reprogramming and maintenance of pluripotency.

Xu P1,2, Wang TT1,3, Liu XZ1,2, Wang NY1,2, Sun LH4, Zhang ZQ1,2, Chen HZ1,2, Lv X1,2, Huang Y1,5, Liu DP6,7.

Author information

1
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
2
Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
3
Central Research Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
4
Center for Experimental Animal Research, Institute of Basic Medical Sciences Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
5
Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
6
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China. liudp@pumc.edu.cn.
7
Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China. liudp@pumc.edu.cn.

Abstract

BACKGROUND:

Mouse somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors known to regulate pluripotency, including Oct4, Sox2, Klf4, and c-Myc. It has been reported that Sirtuin 6 (Sirt6), a member of the sirtuin family of NAD+-dependent protein deacetylases, is involved in embryonic stem cell differentiation. However, whether and how Sirt6 influences epigenetic reprogramming remains unknown.

METHODS:

Mouse embryonic fibroblasts isolated from transgenic Oct4-GFP reporter mice with or without Sirt6 were used for reprogramming by Yamanaka factors. Alkaline phosphatase-positive and OCT4-GFP-positive colony were counted to calculate reprogramming efficiency. OP9 feeder cell co-culture system was used to measure the hematopoietic differentiation from mouse ES and iPS cells. RNA sequencing was measured to identify the differential expressed genes due to loss of Sirt6 in somatic and pluripotent cells.

RESULTS:

In this study, we provide evidence that Sirt6 is involved in mouse somatic reprogramming. We found that loss of function of Sirt6 could significantly decrease reprogramming efficiency. Furthermore, we showed that Sirt6-null iPS-like cell line has intrinsically a differentiation defect even though the establishment of normal self-renewal. Particularly, by performing transcriptome analysis, we observed that several pluripotent transcriptional factors increase in knockout cell line, which explains the underlying loss of pluripotency in Sirt6-null iPS-like cell line.

CONCLUSIONS:

Taken together, we have identified a new regulatory role of Sirt6 in reprogramming and maintenance of pluripotency.

KEYWORDS:

Differentiation; Mouse embryonic fibroblast; Reprogramming; Sirt6

PMID:
30630525
DOI:
10.1186/s13287-018-1109-5
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