An individual based computational model of intestinal crypt fission and its application to predicting unrestrictive growth of the intestinal epithelium.
An individual based computational model of intestinal crypt fission and its application to predicting unrestrictive growth of the intestinal epithelium.
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基于个体的肠隐窝裂变计算模型及其在预测肠上皮无限制生长中的应用。
DOI：
10.1039/c4ib00236a
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Pin C
中科院分区：
文献类型：
--
作者：
Pin C
肠隐窝分裂是一种稳态现象，可在健康成人粘膜中观察到，但它也作为某些肠息肉生长的主要模式发挥病理作用。基于我们以前的基于个体的模型，用于小肠隐窝和体外培养的肠类器官，我们在这里将隐窝分裂建模为基于单个细胞水平的流体力学的萌芽过程，并外推肠上皮生长的预测。在具有丰富潘氏细胞的类器官区域中总是观察到出芽。我们的数据支持一个模型，其中芽是生物力学发起的单干细胞周围的潘氏细胞表现出更大的抵抗粘弹性变形，一个假设支持的单细胞的原子力测量。连续出芽事件之间的时间间隔，模拟的模型和体外，分别为2.84和2.62天。预测的细胞动力学是不受影响的原始隐窝内保留其完整的能力，提供细胞的上皮细胞在整个分裂。在模拟的初级隐窝中，有丝分裂压力迫使芽向上迁移，同时以模拟的1.03天-1和0.99天-1的速度生长成新的突出隐窝。模拟地穴在4.6天内达到最终大小，并需要6.2天才能迁移到主地穴的顶部。次级隐窝的生长与其沿着原隐窝的迁移无关。假设无限制的隐窝分裂和多个出芽事件，肠上皮细胞的最大生长速率为0.10天-1，因此息肉大小增加10倍需要大约22天。这些预测与报道的Apcin肠干细胞丢失后小鼠发生肉眼可见腺瘤的时间一致。
Intestinal crypt fission is a homeostatic phenomenon, observable in healthy adult mucosa, but which also plays a pathological role as the main mode of growth of some intestinal polyps. Building on our previous individual based model for the small intestinal crypt and onin vitrocultured intestinal organoids, we here model crypt fission as a budding process based on fluid mechanics at the individual cell level and extrapolated predictions for growth of the intestinal epithelium. Budding was always observed in regions of organoids with abundant Paneth cells. Our data support a model in which buds are biomechanically initiated by single stem cells surrounded by Paneth cells which exhibit greater resistance to viscoelastic deformation, a hypothesis supported by atomic force measurements of single cells. Time intervals between consecutive budding events, as simulated by the model and observedin vitro, were 2.84 and 2.62 days, respectively. Predicted cell dynamics was unaffected within the original crypt which retained its full capability of providing cells to the epithelium throughout fission. Mitotic pressure in simulated primary crypts forced upward migration of buds, which simultaneously grew into new protruding crypts at a rate equal to 1.03 days-1in simulations and 0.99 days-1in cultured organoids. Simulated crypts reached their final size in 4.6 days, and required 6.2 days to migrate to the top of the primary crypt. The growth of the secondary crypt is independent of its migration along the original crypt. Assuming unrestricted crypt fission and multiple budding events, a maximal growth rate of the intestinal epithelium of 0.10 days-1is predicted and thus approximately 22 days are required for a 10-fold increase of polyp size. These predictions are in agreement with the time reported to develop macroscopic adenomas in mice after loss ofApcin intestinal stem cells.
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影响因子：
24.5
作者：
W. Wong;N. Mandir;R. Goodlad;B. Wong;S. Garcia;S. Lam;N. Wright
通讯作者：
W. Wong;N. Mandir;R. Goodlad;B. Wong;S. Garcia;S. Lam;N. Wright
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：
10.1098/rsta.2010.0173
发表时间：
2010-11
期刊：
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
影响因子：
--
作者：
J. Osborne;A. Walter;S. K. Kershaw;Gary R. Mirams;A. Fletcher;P. Pathmanathan;D. Gavaghan;O. Jensen;P. Maini;H. Byrne
通讯作者：
J. Osborne;A. Walter;S. K. Kershaw;Gary R. Mirams;A. Fletcher;P. Pathmanathan;D. Gavaghan;O. Jensen;P. Maini;H. Byrne
DOI：
10.1111/j.1365-2184.1975.tb01219.x
发表时间：
1975-01-01
期刊：
CELL AND TISSUE KINETICS
影响因子：
--
作者：
CAIRNIE, AB;MILLEN, BH
通讯作者：
MILLEN, BH
影响因子：
64.5
作者：
HENNEBERRY, RC;FISHMAN, PH;FREESE, E
通讯作者：
FREESE, E