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Cell Reprogram. 2015 Dec;17(6):441-52. doi: 10.1089/cell.2015.0039. Epub 2015 Nov 18.

Roles of p53 and ASF1A in the Reprogramming of Sheep Kidney Cells to Pluripotent Cells.

Shi H1,2,3, Fu Q1,2,3, Li G1,3, Ren Y4, Hu S5, Ni W5, Guo F4, Shi M5, Meng L1, Zhang H1, Qiao J1, Guo Z1, Chen C1.

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1 College of Animal Science and Technology, Shihezi University , Shihezi 832003, Xinjiang, China .
2 College of Veterinary Medicine, Xinjiang Agricultural University , Urumqi 830052, Xinjiang, China .
5 These authors contributed equally to this work.
3 College of Medicine, Shihezi University , Shihezi 832003, Xinjiang, China .
4 College of Life Technology, Shihezi University , Shihezi 832003, Xinjiang, China .


Since the first report of induced pluripotent stem cells (iPSCs) by Takahashi and Yamanaka, numerous attempts have been made to derive iPSCs from other species via the ectopic expression of defined factors. Sheep iPSCs (siPSCs) have significant potential for biotechnology and agriculture. Although several groups have described siPSCs, the reprogramming efficiency was extremely low. The exogenous transgenes could be not silenced in the iPSCs, which hampered their development and application. Here, we report that p53 knockdown and antisilencing function 1A (ASF1A) overexpression promoted iPSC generation from sheep kidney cells (SKCs). Compared with transduction with eight human defined transcription factors (Oct4, Sox2, Klf4, c-Myc, Nanog, Lin28, hTERT, and SV40LT), the additional introduction of p53 RNA interference (RNAi) and/or ASF1A in the presence of small-molecule compounds [vitamin C (Vc) and valproic acid (VPA)] greatly improved the efficiency of sheep iPSC generation. The siPSCs exhibited morphological features similar to mouse embryonic stem cells (ESCs) and were positive for alkaline phosphatase and, pluripotent marker genes (Oct4, Nanog, Sox2, Rex1, TRA-1-60, TRA-1-81, and E-cadherin). Furthermore, these cells exhibited a normal karyotype of 54 chromosomes and were able to differentiate into all three germ layers both in vitro and in vivo. Moreover, the exogenous genes were silenced in siPSCs when p53 small hairpin RNA (shRNA) and ASF1A were added. Our results may help to reveal the role of p53 and ASF1A in sheep somatic cell reprogramming and provide an efficient approach to reprogramming sheep somatic cells.

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