Partially Reprogrammed Induced Pluripotent Stem Cells Using MicroRNA Cluster miR-302s in Guangxi Bama Minipig Fibroblasts
Partially Reprogrammed Induced Pluripotent Stem Cells Using MicroRNA Cluster miR-302s in Guangxi Bama Minipig Fibroblasts
复制标题
使用 MicroRNA 簇 miR-302 在广西巴马小型猪成纤维细胞中部分重编程诱导多能干细胞
DOI：
10.1089/cell.2019.0035
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发表时间：
2019
影响因子：
1.6
通讯作者：
Li Xiangping
中科院分区：
文献类型：
--
作者：
Qiao Shuye;Deng Yanfei;Li Sheng;Yang Xiaoling;Shi Deshun;Li Xiangping
猪诱导多能干细胞（piPSC）在再生医学方面具有巨大的应用潜力。单独的 miR-302s 簇已被证明可以将小鼠和人类体细胞重编程为诱导多能干细胞 (iPSC)，无需外源转录因子。然而，尚未有报道称 miR-302 可以单独对大型牲畜的细胞进行重编程。在本研究中，我们利用 miR-302s 簇 (miR-302s-piPSC) 的过表达诱导猪体细胞进入部分重编程的 piPSC，并研究了 miRNA 诱导过程中的早期重编程事件。结果表明，miR-302s-piPSC 表现出多能干细胞的一些特征，包括多能性标记物的表达，特别是内源性 OCT4 的有效激活，以及体外分化为三个胚层。在早期重编程过程中，体细胞首先经历上皮-间质转化，然后经历间质-上皮转化，最终形成miR-302s-piPSC。这些数据首次表明，单因子 miR-302s 成功诱导猪体细胞转化为 miR-302s-piPSC。该研究为大型家畜多能干细胞的诱导提供了新的工具和研究方向。
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 endogenousOCT4—and differentiation to the three germ layersin vitro. 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.