Derivation of Human Trophoblast Stem Cells

Hiroaki Okae, Hidehiro Toh, Tetsuya Sato, Hitoshi Hiura, Sota Takahashi, Kenjiro Shirane, Yuka Kabayama, Mikita Suyama, Hiroyuki Sasaki, Takahiro Arima

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

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. 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.

Original languageEnglish
Pages (from-to)50-63.e6
JournalCell Stem Cell
Volume22
Issue number1
DOIs
Publication statusPublished - 2018 Jan 4

Keywords

  • DNA methylation
  • blastocyst
  • cell fusion
  • epithelial-mesenchymal transition
  • genomic imprinting
  • implantation
  • microRNA
  • placenta
  • transcriptome
  • trophoblast stem cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Derivation of Human Trophoblast Stem Cells'. Together they form a unique fingerprint.

  • Cite this

    Okae, H., Toh, H., Sato, T., Hiura, H., Takahashi, S., Shirane, K., Kabayama, Y., Suyama, M., Sasaki, H., & Arima, T. (2018). Derivation of Human Trophoblast Stem Cells. Cell Stem Cell, 22(1), 50-63.e6. https://doi.org/10.1016/j.stem.2017.11.004