caa a22 4500 445292873 CHVBK 20180317142533.0 cr unu---uuuuu 170323e20100501xx s 000 0 eng 10.1007/s11626-009-9266-6 doi (NATIONALLICENCE)springer-10.1007/s11626-009-9266-6 BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin [Elektronische Daten] [Yohei Hayashi, Miho Furue, Satoshi Tanaka, Michiko Hirose, Noriko Wakisaka, Hiroki Danno, Kiyoshi Ohnuma, Shiho Oeda, Yuko Aihara, Kunio Shiota, Atsuo Ogura, Shoichi Ishiura, Makoto Asashima] 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. The Author(s), 2009 BMP4 nationallicence Smad nationallicence Cdx2 nationallicence Trophoblast nationallicence Mouse embryonic stem cells nationallicence Hayashi Yohei Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut Furue Miho Japanese Collection of Research Bioresources (JCRB) Cell Bank, Laboratory of Cell Culture, Division of Bioresources, National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, 567-0085, Ibaraki, Osaka, Japan aut Tanaka Satoshi Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, 113-8657, Tokyo, Japan aut Hirose Michiko Bioresource Center, RIKEN, 305-0074, Ibaraki, Japan aut Wakisaka Noriko Bioresource Center, RIKEN, 305-0074, Ibaraki, Japan aut Danno Hiroki Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut Ohnuma Kiyoshi Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut Oeda Shiho Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut Aihara Yuko Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut Shiota Kunio Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, 113-8657, Tokyo, Japan aut Ogura Atsuo Bioresource Center, RIKEN, 305-0074, Ibaraki, Japan aut Ishiura Shoichi Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut Asashima Makoto Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/5(2010-05-01), 416-430 1071-2690 46:5<416 2010 46 11626 https://doi.org/10.1007/s11626-009-9266-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11626-009-9266-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hayashi Yohei Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut NATIONALLICENCE 700 1- Furue Miho Japanese Collection of Research Bioresources (JCRB) Cell Bank, Laboratory of Cell Culture, Division of Bioresources, National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, 567-0085, Ibaraki, Osaka, Japan aut NATIONALLICENCE 700 1- Tanaka Satoshi Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, 113-8657, Tokyo, Japan aut NATIONALLICENCE 700 1- Hirose Michiko Bioresource Center, RIKEN, 305-0074, Ibaraki, Japan aut NATIONALLICENCE 700 1- Wakisaka Noriko Bioresource Center, RIKEN, 305-0074, Ibaraki, Japan aut NATIONALLICENCE 700 1- Danno Hiroki Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut NATIONALLICENCE 700 1- Ohnuma Kiyoshi Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut NATIONALLICENCE 700 1- Oeda Shiho Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut NATIONALLICENCE 700 1- Aihara Yuko Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut NATIONALLICENCE 700 1- Shiota Kunio Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, 113-8657, Tokyo, Japan aut NATIONALLICENCE 700 1- Ogura Atsuo Bioresource Center, RIKEN, 305-0074, Ibaraki, Japan aut NATIONALLICENCE 700 1- Ishiura Shoichi Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut NATIONALLICENCE 700 1- Asashima Makoto Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, 153-8902, Tokyo, Japan aut NATIONALLICENCE 773 0- In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/5(2010-05-01), 416-430 1071-2690 46:5<416 2010 46 11626 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer