Volume 21, No 4, Apr 2011

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 21 Issue 4, April 2011: 600-608

ORIGINAL ARTICLES

Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors

Lei Bao^1,*, Lixiazi He^1,*, Jijun Chen¹, Zhao Wu¹, Jing Liao¹, Lingjun Rao¹, Jiangtao Ren¹, Hui Li³, Hui Zhu¹, Lei Qian¹, Yijun Gu¹, Huimin Dai¹, Xun Xu⁵, Jinqiu Zhou², Wen Wang⁵, Chun Cui^1,4 and Lei Xiao^1,4

¹Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

²The State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

³Xiangtan Center Hospital, Hunan 411100, China

⁴College of Animal Sciences, Zhejiang University, Hangzhou 310058, China

⁵CAS-Max Planck Junior Research Group, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China Correspondence: Lei Xiao,(leixiao@sibs.ac.cn, leixiao@zju.edu.cn)

Reprogramming of somatic cells in the enucleated egg made Dolly, the sheep, the first successfully cloned mammal in 1996. However, the mechanism of sheep somatic cell reprogramming has not yet been addressed. Moreover, sheep embryonic stem (ES) cells are still not available, which limits the generation of precise gene-modified sheep. In this study, we report that sheep somatic cells can be directly reprogrammed to induced pluripotent stem (iPS) cells using defined factors (Oct4, Sox2, c-Myc, Klf4, Nanog, Lin28, SV40 large T and hTERT). Our observations indicated that somatic cells from sheep are more difficult to reprogram than somatic cells from other species, in which iPS cells have been reported. We demonstrated that sheep iPS cells express ES cell markers, including alkaline phosphatase, Oct4, Nanog, Sox2, Rex1, stage-specific embryonic antigen-1, TRA-1-60, TRA-1-81 and E-cadherin. Sheep iPS cells exhibited normal karyotypes and were able to differentiate into all three germ layers both in vitro and in teratomas. Our study may help to reveal the mechanism of somatic cell reprogramming in sheep and provide a platform to explore the culture conditions for sheep ES cells. Moreover, sheep iPS cells may be directly used to generate precise gene-modified sheep.

Cell Research (2011) 21:600-608. doi:10.1038/cr.2011.6; published online 11 January 2011

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