Bollas Audrey, Shahriyari Leili
Department of Mathematics, The Ohio State University, Columbus, OH, United States of America.
Mathematical Biosciences Institute, The Ohio State University, Columbus, OH, United States of America.
PLoS One. 2017 Sep 20;12(9):e0184651. doi: 10.1371/journal.pone.0184651. eCollection 2017.
It has been discovered that there are two stem cell groups in the intestinal crypts: central stem cells (CeSCs), which are at the very bottom of the crypt, and border stem cells (BSCs), which are located between CeSCs and transit amplifying cells (TAs). Moreover, backward cell migration from BSCs to CeSCs has been observed. Recently, a bi-compartmental stochastic model, which includes CeSCs and BSCs, has been developed to investigate the probability of two-hit mutant production in the stem cell niche. In this project, we improve this stochastic model by adding the probability of backward cell migration to the model. The model suggests that the probability of two-hit mutant production increases when the frequency of backward cell migration increases. Furthermore, a small non-zero probability of backward cell migration leads to the largest range of optimal values for the frequency of symmetric divisions and the portion of divisions at each stem cell compartment in terms of delaying 2-hit mutant production. Moreover, the probability of two-hit mutant production is more sensitive to the probability of symmetric divisions than to the rate of backward cell migrations. The highest probability of two-hit mutant production corresponds to the case when all stem cell's divisions are asymmetric.
现已发现，肠道隐窝中有两类干细胞群：位于隐窝最底部的中央干细胞（CeSCs），以及位于中央干细胞和过渡增殖细胞（TAs）之间的边缘干细胞（BSCs）。此外，还观察到细胞从边缘干细胞向中央干细胞的逆向迁移。最近，已开发出一种包含中央干细胞和边缘干细胞的双区室随机模型，以研究干细胞生态位中产生双打击突变体的概率。在本项目中，我们通过将细胞逆向迁移的概率添加到模型中对该随机模型进行改进。该模型表明，当逆向细胞迁移频率增加时，产生双打击突变体的概率会增加。此外，就延迟双打击突变体产生而言，非零的小逆向细胞迁移概率会导致对称分裂频率和每个干细胞区室分裂比例的最优值范围最大。而且，产生双打击突变体的概率对对称分裂概率比对逆向细胞迁移速率更敏感。产生双打击突变体的最高概率对应于所有干细胞分裂均为不对称的情况。
