Cell organisation in the colonic crypt: a theoretical comparison of the pedigree and niche concepts.
Cell organisation in the colonic crypt: a theoretical comparison of the pedigree and niche concepts.
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DOI：
10.1371/journal.pone.0073204
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Smith DW
中科院分区：
文献类型：
--
作者：
van der Wath RC;Gardiner BS;Burgess AW;Smith DW
肠粘膜是快速自我更新的上皮细胞的单层，其不仅负责将水和营养物吸收到血流中，而且还充当防止有害微生物进入体内的保护屏障。新的功能性上皮细胞由干细胞及其增殖后代产生。这些干细胞存在于沿着肠道分布的数百万个隐窝（管状凹陷）中。在小鼠中，整个肠上皮每2-3天更换一次（在人类中为3-5天），因此细胞的产生、分化、迁移和周转需要严格调节。这种调节的功能障碍与炎症性肠病以及腺瘤和最终癌性肿瘤的形成密切相关。尽管进行了大量的生物学实验和观察，但结肠隐窝是如何被调节以产生成熟的结肠细胞的仍然不清楚。为了帮助理解细胞在隐窝组织是如何实现的，两个非常不同的概念模型的细胞行为在这里开发，称为“谱系”和“利基”模型。谱系模型提出，隐窝细胞在很大程度上是预先编程的，并且当它们通过常规的细胞分化和增殖成为成熟的结肠细胞时，从环境中获得最小的刺激。小生境模型提出，隐窝细胞主要是受局部微环境沿着隐窝，和预定的细胞行为在其发展中起着微不足道的作用。在本文中，我们提出了一个计算模型，在小鼠的结肠隐窝，这使得成熟的结肠细胞生产的质量和可控性的比较隐窝下运行这两个对比的概念模型的隐窝调节。
The intestinal mucosa is a monolayer of rapidly self-renewing epithelial cells which is not only responsible for absorption of water and nutrients into the bloodstream but also acts as a protective barrier against harmful microbes entering the body. New functional epithelial cells are produced from stem cells, and their proliferating progeny. These stem cells are found within millions of crypts (tubular pits) spaced along the intestinal tract. The entire intestinal epithelium is replaced every 2–3 days in mice (3–5 days in humans) and hence cell production, differentiation, migration and turnover need to be tightly regulated. Malfunctions in this regulation are strongly linked to inflammatory bowel diseases and to the formation of adenomas and ultimately cancerous tumours. Despite a great deal of biological experimentation and observation, precisely how colonic crypts are regulated to produce mature colonocytes remains unclear. To assist in understanding how cell organisation in crypts is achieved, two very different conceptual models of cell behaviour are developed here, referred to as the ‘pedigree’ and the ‘niche’ models. The pedigree model proposes that crypt cells are largely preprogrammed and receive minimal prompting from the environment as they move through a routine of cell differentiation and proliferation to become mature colonocytes. The niche model proposes that crypt cells are primarily influenced by the local microenvironments along the crypt, and that predetermined cell behaviour plays a negligible role in their development. In this paper we present a computational model of colonic crypts in the mouse, which enables a comparison of the quality and controllability of mature coloncyte production by crypts operating under these two contrasting conceptual models of crypt regulation.
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影响因子：
11.2
作者：
Boman, Bruce M.;Fields, Jeremy Z.;Runquist, Olaf A.
通讯作者：
Runquist, Olaf A.
DOI：
10.1111/j.1365-2184.1988.tb00784.x
发表时间：
1988-07-01
期刊：
CELL AND TISSUE KINETICS
影响因子：
--
作者：
LOEFFLER, M;POTTEN, CS;CHWALINSKI, S
通讯作者：
CHWALINSKI, S
DOI：
10.1083/jcb.201009141
发表时间：
2011-03-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Baum B;Georgiou M
通讯作者：
Georgiou M
DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li L;Clevers H
通讯作者：
Clevers H
影响因子：
3.9
作者：
Heath, JP
通讯作者：
Heath, JP