Format

Send to

Choose Destination
Cell Stem Cell. 2018 Jan 4;22(1):50-63.e6. doi: 10.1016/j.stem.2017.11.004. Epub 2017 Dec 14.

Derivation of Human Trophoblast Stem Cells.

Author information

1
Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: okaehiro@m.tohoku.ac.jp.
2
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
3
Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
4
Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
5
Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: tarima@med.tohoku.ac.jp.

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.

KEYWORDS:

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

PMID:
29249463
DOI:
10.1016/j.stem.2017.11.004
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center