Suppression of dsRNA response genes and innate immunity following Oct4, Stella, and Nanos2 overexpression in mouse embryonic fibroblasts

Oct4、Stella 和 Nanos2 在小鼠胚胎成纤维细胞中过表达后对 dsRNA 反应基因和先天免疫的抑制

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作者:Moein Farshchian, Maryam M Matin, Olivier Armant, Dirk Geerts, Mahtab Dastpak, Saeideh Nakhaei-Rad, Massoumeh Tajeran, Amir Jebelli, Mina Shahriyari, Monireh Bahrami, Ali Fallah, Vesal Yaghoobi, Mahdi Mirahmadi, Mohammad Reza Abbaszadegan, Ahmad Reza Bahrami

Abstract

The self-renewal capacity of germline derived stem cells (GSCs) makes them an ideal source for research and use in clinics. Despite the presence of active gene network similarities between embryonic stem cells (ESCs) and GSCs, there are unanswered questions regarding the roles of evolutionary conserved genes in GSCs. To determine the reprogramming potential of germ cell- specific genes, we designed a polycistronic gene cassette expressing Stella, Oct4 and Nanos2 in a lentiviral-based vector. Deep transcriptome analysis showed the activation of a set of pluripotency and germ-cell-specific markers and the downregulation of innate immune system. The global shut down of antiviral genes included MHC class I, interferon response genes and dsRNA 2'-5'-oligoadenylate synthetase are critical pathways that has been affected . Individual expression of each factor highlighted suppressive effect of Nanos2 on genes such as Isg15 and Oasl2. Collectively, to our knowledge this is the first report showing that Nanos2 could be considered as an immunosuppressive factor. Furthermore, our results demonstrate suppression of endogenous retrotransposons that harbor immune response but further analysis require to uncover the correlation between transposon suppression and immune response in germ cell development.

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