Qiao Shuye, Deng Yanfei, Li Sheng, Yang Xiaoling, Shi Deshun, Li Xiangping
State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, China.
Cell Reprogram. 2019 Oct;21(5):229-237. doi: 10.1089/cell.2019.0035. Epub 2019 Sep 3.
Pig-induced pluripotent stem cells (piPSCs) have great potential application in regenerative medicine. The miR-302s cluster alone has been shown to reprogram mouse and human somatic cells into induced pluripotent stem cells (iPSCs) without exogenous transcription factors. However, miR-302s alone have not been reported to reprogram cells in large livestock. In this study, we induced pig somatic cells into partially reprogrammed piPSCs using overexpression of the miR-302s cluster (miR-302s-piPSC) and investigated the early reprogramming events during the miRNA induction process. The results showed that miR-302s-piPSCs exhibited some characteristics of pluripotent stem cells including expression of pluripotency markers-particularly, efficient activation of endogenous -and differentiation to the three germ layers . During the early reprogramming process, somatic cells first underwent epithelial-mesenchymal transition and then mesenchymal-epithelial transition to eventually form miR-302s-piPSCs. These data show, for the first time, that single factor miR-302s successfully induced pig somatic cells into miR-302s-piPSCs. This study provides a new tool and research direction for the induction of pluripotent stem cells in a large livestock.
猪诱导多能干细胞（piPSCs）在再生医学中具有巨大的潜在应用价值。单独的miR - 302s簇已被证明可在无外源性转录因子的情况下将小鼠和人类体细胞重编程为诱导多能干细胞（iPSCs）。然而，尚未有报道称单独的miR - 302s能使大型家畜细胞重编程。在本研究中，我们通过过表达miR - 302s簇（miR - 302s - piPSC）将猪体细胞诱导为部分重编程的piPSCs，并研究了miRNA诱导过程中的早期重编程事件。结果表明，miR - 302s - piPSCs表现出多能干细胞的一些特征，包括多能性标志物的表达——特别是内源性的有效激活——以及向三个胚层的分化。在早期重编程过程中，体细胞首先经历上皮 - 间充质转化，然后经历间充质 - 上皮转化，最终形成miR - 302s - piPSCs。这些数据首次表明，单一因子miR - 302s成功地将猪体细胞诱导为miR - 302s - piPSCs。本研究为大型家畜多能干细胞的诱导提供了一种新工具和研究方向。
