Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Toky, 113-8657, Japan.
The Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.
Sci Rep. 2020 Apr 22;10(1):6827. doi: 10.1038/s41598-020-63602-7.
The placenta forms a maternal-fetal junction that supports many physiological functions such as the supply of nutrition and exchange of gases and wastes. Establishing an in vitro culture model of human and non-human primate trophoblast stem/progenitor cells is important for investigating the process of early placental development and trophoblast differentiation. In this study, we have established five trophoblast stem cell (TSC) lines from cynomolgus monkey blastocysts, named macTSC #1-5. Fibroblast growth factor 4 (FGF4) enhanced proliferation of macTSCs, while other exogenous factors were not required to maintain their undifferentiated state. macTSCs showed a trophoblastic gene expression profile and trophoblast-like DNA methylation status and also exhibited differentiation capacity towards invasive trophoblast cells and multinucleated syncytia. In a xenogeneic chimera assay, these stem cells contributed to trophectoderm (TE) development in the chimeric blastocysts. macTSC are the first primate trophoblast cell lines whose proliferation is promoted by FGF4. These cell lines provide a valuable in vitro culture model to analyze the similarities and differences in placental development between human and non-human primates.
胎盘形成了一个支持许多生理功能的母体-胎儿连接，例如营养供应和气体及废物交换。建立人类和非人类灵长类动物滋养层干细胞/祖细胞的体外培养模型对于研究早期胎盘发育和滋养层分化过程非常重要。在这项研究中，我们从食蟹猴囊胚中建立了五个滋养层干细胞（TSC）系，命名为 macTSC#1-5。成纤维细胞生长因子 4（FGF4）增强了 macTSC 的增殖，而维持其未分化状态则不需要其他外源因子。macTSC 表现出滋养层基因表达谱和滋养层样 DNA 甲基化状态，并且还表现出向侵袭性滋养层细胞和多核合胞体分化的能力。在异种嵌合体测定中，这些干细胞有助于嵌合囊胚的滋养外胚层（TE）发育。macTSC 是第一批由 FGF4 促进增殖的灵长类滋养层细胞系。这些细胞系为分析人类和非人类灵长类动物之间胎盘发育的相似性和差异性提供了有价值的体外培养模型。
