Bending gradients: how the intestinal stem cell gets its home.

Bending gradients: how the intestinal stem cell gets its home.
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DOI:
10.1016/j.cell.2015.03.041
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发表时间:
2015-04-23
期刊:
影响因子:
64.5
通讯作者:
Tabin CJ
Tabin CJ
中科院分区:
生物学1区
文献类型:
--
作者:
Shyer AE;Huycke TR;Lee C;Mahadevan L;Tabin CJ

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我们解决的机制,成人肠干细胞(ISCs)成为本地化的基础上每个绒毛在胚胎发育过程中。我们发现,在肠道发育的早期,增殖的祖细胞表达ISC标记物均匀分布在整个上皮细胞,在鸡和小鼠。然而,随着绒毛的形成,假定的干细胞变得局限于绒毛的基部。这种定位的转变是由上皮和下层间充质之间受机械影响的相互信号传导驱动的。屈曲力在物理上扭曲了形态发生场的形状,从而在每个绒毛的尖端处引起上皮信号的局部最大值,特别是Shh。这诱导了一套高阈值反应基因在底层间充质形成一个信号中心称为“绒毛簇”。绒毛簇信号,特别是Bmp4,反馈到覆盖的上皮上,最终将干细胞限制在每个绒毛的基部。
We address the mechanism by which adult intestinal stem cells (ISCs) become localized to base of each villus during embryonic development. We find that, early in gut development, proliferating progenitors expressing ISC markers are evenly distributed throughout the epithelium, in both the chick and mouse. However as the villi form, the putative stem cells become restricted to the base of the villi. This shift in the localization is driven by mechanically influenced reciprocal signaling between the epithelium and underlying mesenchyme. Buckling forces physically distort the shape of the morphogenic field causing local maxima of epithelial signals, in particular Shh, at the tip of each villus. This induces a suite of high threshold response genes in the underlying mesenchyme to form a signaling center called the “villus cluster.” Villus cluster signals, notably Bmp4, feed back on the overlying epithelium, to ultimately restrict the stem cells to the base of each villus.
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