Lobachevsky P N, Radford I R
Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, Australia.
Cell Prolif. 2006 Oct;39(5):379-402. doi: 10.1111/j.1365-2184.2006.00395.x.
A model of intestinal crypt organization is suggested based on the assumption that stem cells have a finite replicative life span. The model assumes the existence in a crypt of a quiescent ('deep') stem cell and a few more actively cycling ('proximate') stem cells. Monte Carlo computer simulation of published intestinal crypt mutagenesis data is used to test the model. The results of the simulation indicate that stabilization of the crypt mutant phenotype following treatment with external mutagen is consistent with a stem cell replicative life span of about 40 divisions for mouse colon and 90-100 divisions for mouse small intestine, corresponding to a deep stem cell cycle time of about 3.9 and 8.5 weeks for colon and small intestine, respectively. Simulation of the data obtained for human colorectal crypts suggests that the proximate stem cell cycle time is about 80 h, assuming a replicative life span of 50-150 divisions, and that the deep stem cell divides approximately every 30 weeks.
基于干细胞具有有限复制寿命的假设，提出了一种肠隐窝组织模型。该模型假定在一个隐窝中存在一个静止（“深层”）干细胞和一些更活跃循环（“近端”）的干细胞。利用已发表的肠隐窝诱变数据进行蒙特卡罗计算机模拟来测试该模型。模拟结果表明，用外部诱变剂处理后隐窝突变体表型的稳定与小鼠结肠干细胞约40次分裂、小鼠小肠干细胞90 - 100次分裂的复制寿命一致，分别对应结肠和小肠深层干细胞约3.9周和8.5周的细胞周期时间。对人类结直肠隐窝获得的数据进行模拟表明，假设复制寿命为50 - 150次分裂，近端干细胞的细胞周期时间约为80小时，而深层干细胞大约每30周分裂一次。
