弯曲梯度：肠道干细胞如何找到其归属。
Bending gradients: how the intestinal stem cell gets its home.
作者信息
Shyer Amy E, Huycke Tyler R, Lee ChangHee, Mahadevan L, Tabin Clifford J
机构信息
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Physics, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA; Kavli Institute for Nanobio Science and Technology, Harvard University, Cambridge, MA 02138, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Cell. 2015 Apr 23;161(3):569-580. doi: 10.1016/j.cell.2015.03.041. Epub 2015 Apr 9.
We address the mechanism by which adult intestinal stem cells (ISCs) become localized to the 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.
我们研究了成年肠道干细胞（ISC）在胚胎发育过程中定位于每个绒毛基部的机制。我们发现，在肠道发育早期，表达ISC标记的增殖祖细胞在鸡和小鼠的整个上皮中均匀分布。然而，随着绒毛的形成，假定的干细胞被限制在绒毛基部。这种定位的转变是由上皮和下方间充质之间受机械影响的相互信号传导驱动的。屈曲力使形态发生场的形状发生物理扭曲，导致每个绒毛尖端的上皮信号，特别是Shh出现局部最大值。这会诱导下方间充质中的一组高阈值反应基因形成一个称为“绒毛簇”的信号中心。绒毛簇信号，特别是Bmp4，反馈到上方的上皮，最终将干细胞限制在每个绒毛的基部。
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