Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs

被引:159
作者
Lindsley, R. Coleman [1 ]
Gill, Jennifer G. [1 ]
Murphy, Theresa L. [1 ]
Langer, Ellen M. [1 ]
Cai, Mi [1 ]
Mashayekhi, Mona [1 ]
Wang, Wei [3 ]
Niwa, Noriko [3 ]
Nerbonne, Jeanne M. [3 ]
Kyba, Michael [4 ]
Murphy, Kenneth M. [1 ,2 ]
机构
[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA
[4] Univ Texas SW Med Ctr Dallas, Ctr Dev Biol, Dallas, TX 75390 USA
关键词
D O I
10.1016/j.stem.2008.04.004
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Wnt signaling is required for development of mesoderm-derived lineages and expression of transcription factors associated with the primitive streak. In a functional screen, we examined the mesoderm-inducing capacity of transcription factors whose expression was Wnt-dependent in differentiating ESCs. In contrast to many inactive factors, we found that mesoderm posterior 1 (Mesp1) promoted mesoderm development independently of Writ signaling. Transient Mesp1 expression in ESCs promotes changes associated with epithelial-mesenchymal transition (EMT) and induction of Snail, consistent with a role in gastrulation. Mesp1 expression also restricted the potential fates derived from ESCs, generating mesoderm progenitors with cardiovascular, but not hematopoietic, potential. Thus, in addition to its effects on EMT, Mesp1 may be capable of generating the recently identified multipotent cardiovascular progenitor from ESCs in vitro.
引用
收藏
页码:55 / 68
页数:14
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