Neutral dynamics and cell renewal of colonic crypts in homeostatic regime

TL;DR

This paper introduces a detailed compartment model of colonic crypt renewal, incorporating cell classes and stochastic analysis to understand cell dynamics, neutral drift, and mutant clone fixation in homeostasis.

Contribution

It presents a novel compartment model including symmetric stem cell divisions and stochastic analysis for crypt cell renewal and mutation effects.

Findings

Model captures cell population dynamics accurately.

Neutral drift leads to monoclonality in crypts.

Mutant clone fixation effects are analyzed.

Abstract

The self renewal process in colonic crypts is the object of several studies. We present here a new compartment model with the following characteristics: a) We distinguish different classes of cells: stem cells, 6 generations of transit amplifying cells and the differentiated cells. b) In order to take into account the monoclonal character of the crypts in homeostatic regime we include symmetric divisions of the stem cells. We first consider the dynamic differential equations that describe the evolution of the mean values of the populations but the small observed value of the total number of cells involved plus the huge dispersion of experimental data found in the literature leads us to study the stochastic discrete process. This analysis allows us to study fluctuations, the neutral drift that leads to monoclonality and the effects of the fixation of mutant clones.