Abstract
It has been discovered that there are two stem cell groups in the intestinal crypts: central stem cells (CeSCs), which are at the very bottom of the crypt, and border stem cells (BSCs), which are located between CeSCs and transit amplifying cells (TAs). Moreover, backward cell migration from BSCs to CeSCs has been observed. Recently, a bi-compartmental stochastic model, which includes CeSCs and BSCs, has been developed to investigate the probability of two-hit mutant production in the stem cell niche. In this project, we improve this stochastic model by adding the probability of backward cell migration to the model. The model suggests that the probability of two-hit mutant production increases when the frequency of backward cell migration increases. Furthermore, a small non-zero probability of backward cell migration leads to the largest range of optimal values for the frequency of symmetric divisions and the portion of divisions at each stem cell compartment in terms of delaying 2-hit mutant production. Moreover, the probability of two-hit mutant production is more sensitive to the probability of symmetric divisions than to the rate of backward cell migrations. The highest probability of two-hit mutant production corresponds to the case when all stem cell’s divisions are asymmetric.
Highlights
Studying stem cell dynamics is important for determining the origin of many diseases including cancer, and it may suggest ways to obtain optimal treatments for these diseases
We modify that model by adding the probability of backward cell migration from border stem cells (BSCs) to central stem cells (CeSCs)
Note that two dead transit amplifying cells (TAs) could be replaced by divisions of TAs, here we only investigate cell dynamics in the stem cell niche
Summary
Studying stem cell dynamics is important for determining the origin of many diseases including cancer, and it may suggest ways to obtain optimal treatments for these diseases. Scientists are trying to use umbilical cord stem cells (USCs), which are a source of mesenchymal stem cells (HUCMSCs) that promote tissue repair and modulate immune responses, to treat solid tumors. In an in vivo study, the injection of rat umbilical cord SCs (rUSCs) could completely abolish rat mammary carcinomas [3]. Knowledge of stem cell division patterns such as their division and death rates, and the rate at which they divide symmetrically or asymmetrically can suggest ways to alter the stem cell niche in order to minimize the number of mutant cells in a tissue. Moran models, which assume a constant number of cells at each updating time step, are commonly used to study cell
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