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

Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs.
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MESP1协调调节分化ESC中的心血管命运限制和上皮 - 间质转变。

DOI:
10.1016/j.stem.2008.04.004
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发表时间:
2008-07-03
期刊:
影响因子:
23.9
通讯作者:
Murphy, Kenneth M.
Murphy, Kenneth M.
中科院分区:
医学1区
文献类型:
--
作者:
Lindsley, R. Coleman;Gill, Jennifer G.;Murphy, Theresa L.;Langer, Ellen M.;Cai, Mi;Mashayekhi, Mona;Wang, Wei;Niwa, Noriko;Nerbonne, Jeanne M.;Kyba, Michael;Murphy, Kenneth M.

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WNT信号对于中胚层起源的谱系的发展和与原始条纹相关的转录因子的表达是必需的。在功能筛选中,我们检测了转录因子的中胚层诱导能力,这些转录因子的表达依赖于Wnt在分化ESCs中的作用。与许多不活跃的因素相比,我们发现中胚层后1(Mesp1)促进了中胚层的发育,而不依赖于Wnt信号。在ESCs中瞬时表达Mesp1促进了与上皮-间充质转化(EMT)相关的变化和Snai1的诱导,这与原肠形成中的作用一致。Mesp1的表达也限制了来自ESCs的潜在命运,产生了具有心血管而不是造血潜能的中胚层祖细胞。因此,除了对EMT的影响外,Mesp1可能还能在体外从ESCs中产生最近发现的多潜能心血管祖细胞。
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 Wnt signaling. Transient Mesp1 expression in ESCs promotes changes associated with epithelial-mesenchymal transition (EMT) and induction of Snai1, 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.
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