Expansion of mutant stem cell populations in the human colon
Expansion of mutant stem cell populations in the human colon
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DOI：
10.1006/jtbi.1996.0034
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发表时间：
1996-02-21
影响因子：
2
通讯作者：
Bjerknes, M
中科院分区：
文献类型：
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作者：
Bjerknes, M
一般来说，假定结肠上皮干细胞是处于招致导致癌的一系列体细胞突变的风险中的主要细胞类型，因为所有其他上皮细胞类型都是短命的。突变干细胞克隆扩增增加了后续突变的风险，因此是致癌的潜在重要步骤。干细胞位于结肠隐窝中，上皮的简单管状折叠，因此计数隐窝提供了确定干细胞数量的间接方法。已知正常隐窝群体通过隐窝复制过程扩增，并且认为这导致上皮干细胞群体的相应扩增。一个简单的数学模型的人口动态的正常和突变的隐窝（含有突变的干细胞的隐窝）的开发和用于估计的突变的干细胞群体的相对扩增率的下限。该模型预测，如果突变和正常的隐窝人口扩大以相同的速度，如果突变率相对于增长速度较小，那么由一个单一的突变隐窝组成的突变隐窝集群的分数应稳步下降，随着年龄的一半。异常隐窝是人类结肠中容易识别的病变，其经常被证明含有K-ras和偶尔APC基因突变的细胞。应用该模型对异常隐窝簇大小的最新计数表明，异常隐窝群体和所包含的突变干细胞群体的扩增速度比正常情况快得多。(C)1996年学术出版社
In general, it is presumed that colonic epithelial stem cells are the principal cell type at risk of incurring the series of somatic mutations leading to carcinoma, since all other epithelial cell types are short-lived. Mutant stem cell clonal expansion increases the risk for subsequent mutations and is therefore a potentially important step in carcinogenesis. The stem cells reside in colonic crypts, simple tubular foldings of the epithelium, and thus counting crypts provides an indirect means to determine stem cell numbers. The normal crypt population is known to expand through a process of crypt replication and this is thought to result in a corresponding expansion of the epithelial stem cell population. A simple mathematical model of the population dynamics of normal and mutant crypts (crypts containing mutant stem cells) is developed and used to estimate a lower bound on the relative rate of expansion of the mutant stem cell population. The model predicts that if mutant and normal crypt populations expand at the same rate, and if the mutation rate is small relative to the rate of growth, then the fraction of clusters of mutant crypts composed of only a single mutant crypt should steadily decrease with age towards one-half. Aberrant crypts are easily recognizable lesions in human colon which have frequently been shown to contain cells with K-ras and occasionally APC gene mutations. Application of the model to recent counts of aberrant crypt cluster sizes indicate that the aberrant crypt population, and the contained mutant stem cell population, is expanding substantially faster than normal. (C) 1996 Academic Press Limited