Stem Cells Dev. 2018 Apr 10. doi: 10.1089/scd.2018.0047. [Epub ahead of print]

Reprogramming p53-deficient germline stem cells into pluripotent state by Nanog.

Feng Y¹, Ning Y², Lin X³, Zhang D⁴, Liao S⁵, Zheng C⁶, Chen J⁷, Wang Y⁸, Ma L⁹, Xie D¹⁰, Han C¹¹.

Abstract

Cultured mouse spermatogonial stem cells (GSCs), revert back to pluripotent state either spontaneously or upon being modified genetically. However, the reprogramming efficiencies are low, and the underlying mechanism remains poorly understood. In the present study, we conducted transcriptomic analysis and found that many transcription factors and epigenetic modifiers were differentially expressed between GSCs and ESCs. We failed in reprogramming GSCs to pluripotent state using the Yamanaka 4 Factors but succeeded when Nanog and Tet1 were included. More importantly, reprogramming was also achieved with Nanog alone in a p53-deficient GSC line with an efficiency of 0.02‰. These GSC-derived-iPSCs possessed in vitro and in vivo differentiation abilities despite of low rate of chimera formation, which might be caused by abnormal methylation in certain paternally imprinted genes. Together, these results show that GSCs can be reprogramed to pluripotent state via multiple avenues and contribute to our understanding of the mechanisms of GSC reprogramming.