BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin.
BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin.
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DOI：
10.1007/s11626-009-9266-6
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发表时间：
2010-05
影响因子：
2.1
通讯作者：
Asashima, Makoto
中科院分区：
文献类型：
--
作者：
Hayashi, Yohei;Furue, Miho Kusuda;Tanaka, Satoshi;Hirose, Michiko;Wakisaka, Noriko;Danno, Hiroki;Ohnuma, Kiyoshi;Oeda, Shiho;Aihara, Yuko;Shiota, Kunio;Ogura, Atsuo;Ishiura, Shoichi;Asashima, Makoto
由于小鼠胚胎干细胞（mESC）在注射到胚泡中时不有助于胚外胎盘的形成，因此认为mESC不分化为滋养层，而人胚胎干细胞（hESC）在体外暴露于骨形态发生蛋白4（BMP 4）时可以表达滋养层标志物。为了测试mESC是否具有分化成滋养层的潜力，我们在限定的单层培养条件下评估了BMP 4对mESC的作用。滋养层特异性转录因子如Cdx 2、Dlx 3、Esx 1、Gata 3、Hand 1、Mash 2和Plx 1的表达在BMP 4处理的分化细胞中特异性上调，并且这些细胞表达滋养层标志物。这些结果表明，在确定的培养条件下，BMP 4处理使mESC分化为滋养层。这种分化被通常用于mESC培养的血清或白血病抑制因子抑制。此外，我们还研究了BMP-4介导的mESC向滋养层细胞分化的机制。我们的研究结果表明，BMP 4激活的Smad通路诱导Cdx 2表达，这在滋养层细胞分化中起着至关重要的作用，通过结合Smad蛋白的Cdx 2基因组增强子序列。我们的研究结果表明，有一个共同的分子机制hESC和mESC分化为滋养层细胞。
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.
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影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
影响因子：
23.9
作者：
Hayashi K;de Sousa Lopes SMC;Tang F;Lao K;Surani MA
通讯作者：
Surani MA
影响因子：
5.2
作者：
Hayashi, Yohei;Furue, Miho Kusuda;Asashima, Makoto
通讯作者：
Asashima, Makoto
影响因子：
30.8
作者：
Anson-Cartwright, L;Dawson, K;Cross, JC
通讯作者：
Cross, JC
影响因子：
10.5
作者：
LESCISIN, KR;VARMUZA, S;ROSSANT, J
通讯作者：
ROSSANT, J