Zhang Wei, Pei Yangli, Zhong Liang, Wen Bingqiang, Cao Suying, Han Jianyong
State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.
College of Animal Science and Technology, Beijing University of Agriculture, Beijing, China.
PLoS One. 2015 Apr 20;10(4):e0124562. doi: 10.1371/journal.pone.0124562. eCollection 2015.
The domestic pig is an excellent animal model for stem cell research and clinical medicine. There is still no suitable culture condition to generate authentic porcine embryonic stem cells (pESCs) and high quality porcine induced pluripotent stem cells (piPSCs). In this study, we found that culture conditions affected pluripotent and metabolic features of piPSCs. Using defined human embryonic stem cell (hESC) and mouse ESC (mESC) culture conditions, we generated two types of piPSCs, one of which was morphologically similar to hESCs (here called hpiPSCs), the other resembled mESCs (here called mpiPSCs). Transcriptome analysis and signaling pathway inhibition results suggested that mpiPSCs shared more of mESC signaling pathways, such as the BMP pathway and JAK/STAT pathway and hpiPSCs shared more hESC signaling pathways, such as the FGF pathway. Importantly, the mpiPSCs performed embryonic chimera incorporation more efficiently than the hpiPSCs did. In addition, the mpiPSCs showed mitochondrial features of naive ESCs and lipid droplets accumulation. These evidences may facilitate understanding of the gene regulation network and metabolism in piPSCs and promote derivation of bona fide pESCs for translational medicine.
家猪是干细胞研究和临床医学的优良动物模型。目前仍没有合适的培养条件来生成真正的猪胚胎干细胞（pESCs）和高质量的猪诱导多能干细胞（piPSCs）。在本研究中，我们发现培养条件会影响piPSCs的多能性和代谢特征。利用已定义的人类胚胎干细胞（hESC）和小鼠胚胎干细胞（mESC）培养条件，我们生成了两种类型的piPSCs，其中一种在形态上与hESCs相似（此处称为hpiPSCs），另一种与mESCs相似（此处称为mpiPSCs）。转录组分析和信号通路抑制结果表明，mpiPSCs共享更多的mESC信号通路，如BMP通路和JAK/STAT通路，而hpiPSCs共享更多的hESC信号通路，如FGF通路。重要的是，mpiPSCs在胚胎嵌合体整合方面比hpiPSCs更有效。此外，mpiPSCs表现出原始胚胎干细胞的线粒体特征和脂滴积累。这些证据可能有助于理解piPSCs中的基因调控网络和代谢，并促进用于转化医学的真正pESCs的衍生。
