BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin

Yohei Hayashi, Miho Kusuda Furue, Satoshi Tanaka, Michiko Hirose, Noriko Wakisaka, Hiroki Danno, Kiyoshi Ohnuma, Shiho Oeda, Yuko Aihara, Kunio Shiota, Atsuo Ogura, Shoichi Ishiura, Makoto Asashima

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Because mouse embryonic stem cells (mESCs) do not contribute to the formation of extraembryonic placenta when they are injected into blastocysts, it is believed that mESCs do not differentiate into trophoblast whereas human embryonic stem cells (hESCs) can express trophoblast markers when exposed to bone morphogenetic protein 4 (BMP4) in vitro. To test whether mESCs have the potential to differentiate into trophoblast, we assessed the effect of BMP4 on mESCs in a defined monolayer culture condition. The expression of trophoblast-specific transcription factors such as Cdx2, Dlx3, Esx1, Gata3, Hand1, Mash2, and Plx1 was specifically upregulated in the BMP4-treated differentiated cells, and these cells expressed trophoblast markers. These results suggest that BMP4 treatment in defined culture conditions enabled mESCs to differentiate into trophoblast. This differentiation was inhibited by serum or leukemia inhibitory factor, which are generally used for mESC culture. In addition, we studied the mechanism underlying BMP4-directed mESC differentiation into trophoblast. Our results showed that BMP4 activates the Smad pathway in mESCs inducing Cdx2 expression, which plays a crucial role in trophoblast differentiation, through the binding of Smad protein to the Cdx2 genomic enhancer sequence. Our findings imply that there is a common molecular mechanism underlying hESC and mESC differentiation into trophoblast.

Original languageEnglish
Pages (from-to)416-430
Number of pages15
JournalIn Vitro Cellular and Developmental Biology - Animal
Volume46
Issue number5
DOIs
Publication statusPublished - 2010 May
Externally publishedYes

Keywords

  • BMP4
  • Cdx2
  • Mouse embryonic stem cells
  • Smad
  • Trophoblast

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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  • Cite this

    Hayashi, Y., Furue, M. K., Tanaka, S., Hirose, M., Wakisaka, N., Danno, H., Ohnuma, K., Oeda, S., Aihara, Y., Shiota, K., Ogura, A., Ishiura, S., & Asashima, M. (2010). BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin. In Vitro Cellular and Developmental Biology - Animal, 46(5), 416-430. https://doi.org/10.1007/s11626-009-9266-6