The role of cell location and spatial gradients in the evolutionary dynamics of colon and intestinal crypts.

ABSTRACT:

Background

Colon and intestinal crypts serve as an important model system for adult stem cell proliferation and differentiation. We develop a spatial stochastic model to study the rate of somatic evolution in a normal crypt, focusing on the production of two-hit mutants that inactivate a tumor suppressor gene. We investigate the effect of cell division pattern along the crypt on mutant production, assuming that the division rate of each cell depends on its location.

Results

We find that higher probability of division at the bottom of the crypt, where the stem cells are located, leads to a higher rate of double-hit mutant production. The optimal case for delaying mutations occurs when most of the cell divisions happen at the top of the crypt. We further consider an optimizati

SUBMITTER: Shahriyari L 

PROVIDER: S-EPMC4994304 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature