Derivation of Human Trophoblast Stem Cells

• Published in: Cell stem cell Vol. 22; no. 1; pp. 50 - 63.e6
• Main Authors: Okae, Hiroaki, Toh, Hidehiro, Sato, Tetsuya, Hiura, Hitoshi, Takahashi, Sota, Shirane, Kenjiro, Kabayama, Yuka, Suyama, Mikita, Sasaki, Hiroyuki, Arima, Takahiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.01.2018
• Subjects: Animals; blastocyst; Blastocyst - cytology; Cell Differentiation; cell fusion; Cell Proliferation; Cells, Cultured; DNA methylation; DNA Methylation - genetics; epithelial-mesenchymal transition; Gene Expression Profiling; genomic imprinting; Humans; implantation; Male; Mice, SCID; microRNA; placenta; Stem Cells - cytology; Stem Cells - metabolism; transcriptome; Transcriptome - genetics; trophoblast stem cell; Trophoblasts - cytology; Trophoblasts - metabolism; implantation; cell fusion; transcriptome; DNA methylation; blastocyst; placenta; microRNA; epithelial-mesenchymal transition; genomic imprinting; trophoblast stem cell
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2017.11.004

Trophoblast cells play an essential role in the interactions between the fetus and mother. Mouse trophoblast stem (TS) cells have been derived and used as the best in vitro model for molecular and functional analysis of mouse trophoblast lineages, but attempts to derive human TS cells have so far been unsuccessful. Here we show that activation of Wingless/Integrated (Wnt) and EGF and inhibition of TGF-β, histone deacetylase (HDAC), and Rho-associated protein kinase (ROCK) enable long-term culture of human villous cytotrophoblast (CT) cells. The resulting cell lines have the capacity to give rise to the three major trophoblast lineages, which show transcriptomes similar to those of the corresponding primary trophoblast cells. Importantly, equivalent cell lines can be derived from human blastocysts. Our data strongly suggest that the CT- and blastocyst-derived cell lines are human TS cells, which will provide a powerful tool to study human trophoblast development and function. [Display omitted] •Human TS cells have the capacity to give rise to the three major trophoblast lineages•Human TS and primary trophoblast cells have similar transcriptomes and methylomes•Human TS cells injected into mice mimic trophoblast invasion during implantation•Signaling pathways maintaining human and mouse TS cells are substantially different Trophoblast cells are specialized cells in the placenta that mediate the interactions between the fetus and mother. Okae et al. report the derivation of human trophoblast stem cells from blastocysts and early placentas, which will provide a powerful tool to study human placental development and function.