Wei Yanxing, Zhou Xiaohua, Huang Wenhao, Long Ping, Xiao Lu, Zhang Tian, Zhong Mei, Pan Guangjin, Ma Yanlin, Yu Yanhong
Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510530, China.
CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, 510530, China.
Placenta. 2017 Mar;51:28-37. doi: 10.1016/j.placenta.2017.01.121. Epub 2017 Jan 20.
Despite the high incidence of trophoblast-related diseases, the molecular mechanism of inadequate early trophoblast development is still unclear due to the lack of an appropriate cellular model in vitro. In the present study, we reprogrammed the amniotic cells to be induced pluripotent stem cells (iPSCs) via a non-virus and non-integrated method and subsequently differentiated them into trophoblast-like cells by a modified BMP4 strategy in E6 medium. Compared with the previously studied trophoblast-like cells from ESCs, the iPSCs derived trophoblast-like cells behave similarly in terms of gene expression profiles and biofunctions. Also we confirmed the differentiating tendency from iPSCs to be syncytiotrophoblasts-like cells might be caused by inappropriate differentiating oxygen condition. Additionally, we preliminarily indicated in vitro "artificial" differentiation of iPSCs also undergoing a possible trophoblastic stem cell stage, as witnessed in vivo. In conclusion, we provided an in vitro cellular model to study early trophoblast development for specific individual, by using the feasible amnion.
尽管滋养层相关疾病的发病率很高,但由于缺乏合适的体外细胞模型,早期滋养层发育不足的分子机制仍不清楚。在本研究中,我们通过非病毒和非整合方法将羊膜细胞重编程为诱导多能干细胞(iPSC),随后在E6培养基中通过改良的BMP4策略将它们分化为滋养层样细胞。与先前研究的来自胚胎干细胞的滋养层样细胞相比,iPSC来源的滋养层样细胞在基因表达谱和生物学功能方面表现相似。我们还证实,iPSC向合体滋养层样细胞的分化趋势可能是由不适当的分化氧气条件引起的。此外,我们初步表明,iPSC在体外的“人工”分化也经历了一个可能的滋养层干细胞阶段,这在体内也有体现。总之,我们通过使用可行的羊膜提供了一个体外细胞模型,用于研究特定个体的早期滋养层发育。