A late requirement for Wnt and FGF signaling during activin-induced formation of foregut endoderm from mouse embryonic stem cells.
A late requirement for Wnt and FGF signaling during activin-induced formation of foregut endoderm from mouse embryonic stem cells.
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DOI：
10.1016/j.ydbio.2009.03.026
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发表时间：
2009-06-15
影响因子：
2.7
通讯作者：
Serup, Palle
中科院分区：
文献类型：
--
作者：
Hansson, Mattias;Olesen, Dorthe R.;Peterslund, Janny M. L.;Engberg, Nina;Kahn, Morten;Winzi, Maria;Klein, Tino;Maddox-Hyttel, Poul;Serup, Palle
在这里，我们研究了BMP、Wnt和FGF信号如何调节激活素诱导的小鼠ES细胞在贴壁单培养中生长的特定条件下的中内胚层分化。我们监测含有报告基因的ES细胞以寻找原始条纹(PS)及其后代的标记，并扩展先前关于激活素浓度增加的能力的发现，以逐步诱导更多的ES细胞后代走向原始条纹(PS)和内胚层命运。我们发现，随着激活素浓度的增加，表达Sox17和GSC的细胞数量增加，而在激活素浓度最低时，表达T的细胞数量最多。BMP4可以阻止激活素诱导的GSC和其他前向标志的表达，从而诱导T的表达和随后的中胚层发育。我们发现，只有在激活素诱导的表达Sox17的内皮细胞发育的后期阶段，才需要规范的Wnt信号。此外，在贴壁培养中，Dkk1处理在抑制Sox17+内皮细胞的发育方面不如聚集培养中的有效，并且似乎比激活素介导的诱导更有效地抑制结节介导的Sox17+细胞的诱导。值得注意的是，激活素诱导的GSC-GFP+细胞似乎不能抑制经典的Wnt信号，但显示出对早期和晚期的成纤维细胞生长因子信号的依赖。此外，在激活素诱导Sox17+细胞的过程中，我们发现后期依赖于成纤维细胞生长因子信号，而骨形态发生蛋白4诱导的T细胞在贴壁培养中需要成纤维细胞生长因子信号，而不是聚集培养。最后，我们证明了激活素诱导的小鼠ES细胞来源的最终内胚层在体内可以整合到发育中的前肠内皮细胞中，并在体外进一步培养后具有主要的前肠特征。
Here we examine how BMP, Wnt, and FGF signaling modulate activin-induced mesendodermal differentiation of mouse ES cells grown under defined conditions in adherent monoculture. We monitor ES cells containing reporter genes for markers of primitive streak (PS) and its progeny and extend previous findings on the ability of increasing concentrations of activin to progressively induce more ES cell progeny to anterior PS and endodermal fates. We find that the number of Sox17- and Gsc-expressing cells increases with increasing activin concentration while the highest number of T-expressing cells is found at the lowest activin concentration. The expression of Gsc and other anterior markers induced by activin is prevented by treatment with BMP4, which induces T expression and subsequent mesodermal development. We show that canonical Wnt-signaling is required only during late stages of activin-induced development of Sox17-expressing endodermal cells. Furthermore, Dkk1 treatment is less effective in reducing development of Sox17+ endodermal cells in adherent culture than in aggregate culture and appears to inhibit nodal-mediated induction of Sox17+ cells more effectively than activin-mediated induction. Notably, activin-induction of Gsc-GFP+ cells appears refractory to inhibition of canonical Wnt signaling but shows a dependence on early as well as late FGF signaling. Additionally, we find a late dependence on FGF signaling during induction of Sox17+ cells by activin while BMP4-induced T expression requires FGF signaling in adherent but not aggregate culture. Lastly, we demonstrate that activin-induced definitive endoderm derived from mouse ES cells can incorporate into the developing foregut endoderm in vivo and adopt a mostly anterior foregut character after further culture in vitro.
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影响因子：
11.8
作者：
Ben-Haim, Nadav;Lu, Cindy;Constam, Daniel B.
通讯作者：
Constam, Daniel B.
DOI：
10.1002/dvg.1020170105
发表时间：
1995-01-01
期刊：
DEVELOPMENTAL GENETICS
影响因子：
--
作者：
CAREY, FJ;LINNEY, EA;PEDERSEN, RA
通讯作者：
PEDERSEN, RA
影响因子：
2.5
作者：
BECK, F;ERLER, T;JAMES, R
通讯作者：
JAMES, R
影响因子：
3.2
作者：
Ahnfelt-Ronne, Jonas;Jorgensen, Mette C.;Hecksher-Sorensen, Jacob
通讯作者：
Hecksher-Sorensen, Jacob
影响因子：
64.5
作者：
Dyson, S;Gurdon, JB
通讯作者：
Gurdon, JB