Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Biophys J. 2010 Aug 4;99(3):716-25. doi: 10.1016/j.bpj.2010.05.016.
Experimental data (e.g., genetic lineage and cell population studies) on intestinal crypts reveal that regulatory features of crypt behavior, such as control via morphogen gradients, are remarkably well conserved among numerous organisms (e.g., from mouse and rat to human) and throughout the different regions of the small and large intestines. In this article, we construct a partial differential equation model of a single colonic crypt that describes the spatial distribution of Wnt pathway proteins along the crypt axis. The novelty of our continuum model is that it is based upon assumptions that can be directly related to processes at the cellular and subcellular scales. We use the model to predict how the distributions of Wnt pathway proteins are affected by mutations. The model is then extended to investigate how mutant cell populations can invade neighboring crypts. The model simulations suggest that cell crowding caused by increased proliferation and decreased cell loss may be sufficient for a mutant cell population to colonize a neighboring healthy crypt.
肠道隐窝的实验数据（例如遗传谱系和细胞群体研究）表明，隐窝行为的调节特征，如形态发生梯度的控制，在许多生物体（例如，从老鼠到人类）和小肠和大肠的不同区域中都得到了很好的保守。在本文中，我们构建了一个描述沿隐窝轴分布的 Wnt 途径蛋白的单个结肠隐窝的偏微分方程模型。我们的连续体模型的新颖之处在于，它基于可以直接与细胞和亚细胞尺度上的过程相关的假设。我们使用该模型来预测 Wnt 途径蛋白的分布如何受到突变的影响。然后，该模型被扩展到研究突变细胞群体如何侵入相邻的隐窝。模型模拟表明，由于增殖增加和细胞丢失减少引起的细胞拥挤可能足以使突变细胞群体殖民相邻的健康隐窝。
