Biomedical Research Group, Applied Mathematics Department, University of Waterloo, Waterloo, ON, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Bull Math Biol. 2018 Sep;80(9):2273-2305. doi: 10.1007/s11538-018-0457-8. Epub 2018 Jul 5.
Colon and intestinal crypts have been widely chosen to study cell dynamics because of their fairly simple structures. In the colon and intestinal crypts, stem cells (SCs) are located at very bottom of the crypt, fully differentiated cells (FDs) are located in the top of the crypt, and transit-amplifying cells (TAs) are in the middle of the crypt between FDs and SCs. Recently, it has been discovered that there are two types of stem cells in the intestinal crypts: central stem cells (CeSCs) and border stem cells. To investigate dynamics of mutants in colon and intestinal crypts, we develop a four-compartmental stochastic model, which includes two SC compartments, and TAs and FDs compartments. We calculate the probability of the progeny of marked or mutant cells located at each of these compartments taking over the entire crypt or being washed out from the crypt. We found that the progeny of CeSCs will take over the entire crypt with a probability close to one. Interestingly, the progeny of advantageous mutant TAs and FDs will be washed out faster than disadvantageous mutants. Saliently, the model predicts that the time that the progeny of wild-type central stem cells will take over the mouse intestinal crypt is around 60 days, which is in perfect agreement with an experimental observation.
由于结肠和肠隐窝具有相对简单的结构，因此它们被广泛用于研究细胞动力学。在结肠和肠隐窝中，干细胞（SCs）位于隐窝的底部，完全分化的细胞（FDs）位于隐窝的顶部，过渡扩增细胞（TAs）位于 FD 和 SC 之间的隐窝中部。最近，人们发现肠隐窝中存在两种类型的干细胞：中央干细胞（CeSCs）和边界干细胞。为了研究结肠和肠隐窝中突变体的动力学，我们开发了一个四室随机模型，该模型包括两个 SC 室以及 TAs 和 FDs 室。我们计算了标记或突变细胞的后代位于这些室中的每个室中接管整个隐窝或从隐窝中冲洗掉的概率。我们发现，CeSCs 的后代接管整个隐窝的概率接近 1。有趣的是，有利突变 TAs 和 FDs 的后代会比不利突变体更快地被冲洗掉。值得注意的是，该模型预测野生型中央干细胞的后代接管小鼠肠隐窝的时间约为 60 天，这与实验观察结果完全一致。
