期刊
CELL STEM CELL
卷 9, 期 2, 页码 144-155出版社
CELL PRESS
DOI: 10.1016/j.stem.2011.06.015
关键词
-
资金
- EU [HEALTH-F4-2009-223485/PluriSys]
- MRC
- Evelyn Trust
- Cambridge Hospitals National Institute for Health Research Biomedical Research Centre
- Fundacao para a Ciencia e a Tecnologia, Portugal
- British Heart Foundation
- Centre for Trophoblast Research
- Welcome Trust
- MRC [G0800784, G0600275, MC_U117597140, G1000847] Funding Source: UKRI
- British Heart Foundation [FS/10/022/28262] Funding Source: researchfish
- Medical Research Council [G0800784B, MC_U117597140, G1000847, G0800784, G0600275] Funding Source: researchfish
BMP is thought to induce hESC differentiation toward multiple lineages including mesoderm and trophoblast. The BMP-induced trophoblast phenotype is a long-standing paradox in stem cell biology. Here we readdressed BMP function in hESCs and mouse epiblast-derived cells. We found that BMP4 cooperates with FGF2 (via ERK) to induce mesoderm and to inhibit endoderm differentiation. These conditions induced cells with high levels of BRACHYURY (BRA) that coexpressed CDX2. BRA was necessary for and preceded CDX2 expression; both genes were essential for expression not only of mesodermal genes but also of trophoblast-associated genes. Maximal expression of the latter was seen in the absence of FGF but these cells coexpressed mesodermal genes and moreover they differed in cell surface and epigenetic properties from placental trophoblast. We conclude that BMP induces human and mouse pluripotent stem cells primarily to form mesoderm, rather than trophoblast, acting through BRA and CDX2.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据