Intestinal Cell Proliferation. I. A Comprehensive Model of Steady‐State Proliferation In the Crypt
Intestinal Cell Proliferation. I. A Comprehensive Model of Steady‐State Proliferation In the Crypt
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肠细胞增殖。 I. 隐窝内稳态增殖的综合模型
DOI：
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发表时间：
1986
期刊：
影响因子：
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通讯作者：
S. Chwalinski
中科院分区：
文献类型：
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作者：
M. Loeffler;R. Stein;H. Wichmann;C. Potten;P. Kaur;S. Chwalinski
抽象的。对小鼠小肠隐窝中的细胞替换进行了研究，并在稳态条件下进行了数学建模。这个系统有大量的信息，如细胞周期时间、S时相持续时间、每日细胞生产率、潘氏细胞分布等。本工作的目的是同时考虑尽可能多的这些数据，并根据单个细胞的行为建立一个充分解释这些数据的模型。已经开发出一个简单的地穴数学表示法。这包括每个隐窝16个干细胞(T_c=16小时，T_s=9小时)，以及成熟前的四次传代细胞分裂(T_c=11-12小时，T_s=8小时)。被认为测试模型的实验数据是LI和关于类似标记的单元格的垂直运行次数的数据。所有数据均在09.00小时给予25μCi[~H]TdR后从回肠获取。已经考虑了许多可供选择的假设，要么接受要么拒绝。两个可供选择的细胞位移模型概念同样很好地解释了数据。一种依赖于强烈的局部细胞世代年龄决定，而另一种则可以适应任何弱的局部细胞置换过程，并结合地穴中部的环境截止决定因素。这两个模型都提供了对数据的新解释，例如，可以从运行数据中得出相邻柱子之间的某些横向细胞交换速率(每天总共420个细胞分裂，每个隐窝每天250到350个)，而LI数据提供了关于维持隐窝中与位置相关的年龄顺序所涉及的机制的信息。
Abstract. Cell replacement in the crypt of the murine small intestine has been studied and modelled mathematically under steady‐state conditions. A great deal of information is available for this system, e.g. cell cycle times, S phase durations, the rate of daily cell production, the Paneth cell distribution etc. the purpose of the present work was to consider simultaneously as much of these data as possible and to formulate a model based upon the behaviour of individual cells which adequately accounted for them. A simple mathematical representation of the crypt has been developed. This consists of sixteen stem cells per crypt (Tc= 16 hr, Ts= 9 hr), and four subsequent transit cell divisions (Tc= 11 to 12 hr, Ts= 8 hr) before maturation. Experimental data considered to test the modelling were LI and data on the number of vertical runs of similarly labelled cells. All data were obtained from the ileum after 25 μCi [3H]TdR given at 09.00 hours. A number of alternative assumptions have been considered and either accepted or rejected. Two alternative model concepts of cell displacement explain the data equally well. One is dependent upon strong local cell generation age determinance while the other could accommodate any weak local cell displacement process in conjunction with an environmental cut‐off determinant at the middle of the crypt. Both models provide new interpretations of the data, e.g. certain rates of lateral cell exchange between neighbouring columns (250 to 350 per crypt per day out of a total of 420 cell divisions per day) can be concluded from run data, while LI data provide information about the mechanisms involved in maintaining a position‐related age order in the crypt.