Stochastic stem cell models with mutation: A comparison of asymmetric and symmetric divisions

TL;DR

This paper compares stochastic models of asymmetric and symmetric stem cell divisions with mutations, revealing that symmetric division exhibits higher fluctuation and the differences are more pronounced at lower mutation rates, emphasizing the role of stochasticity.

Contribution

The study provides a rigorous mathematical comparison of asymmetric and symmetric stem cell division models, highlighting differences in fluctuation and the impact of mutation rates.

Findings

Both models have the same average behavior.

Symmetric division shows higher fluctuation than asymmetric.

Differences are more significant at lower mutation rates.

Abstract

In order to fulfill cell proliferation and differentiation through cellular hierarchy, stem cells can undergo either asymmetric or symmetric divisions. Recent studies pay special attention to the effect of different modes of stem cell division on the lifetime risk of cancer, and report that symmetric division is more beneficial to delay the onset of cancer. The fate uncertainty of symmetric division is considered to be the reason for the cancer-delaying effect. In this paper we compare asymmetric and symmetric divisions of stem cells via studying stochastic stem cell models with mutations. Specially, by using rigorous mathematical analysis we find that both asymmetric and symmetric models show the same statistical average, but symmetric model shows higher fluctuation than asymmetric model. We further show that the difference between the two models would be more remarkable for lower mutation rates. Our work quantifies the uncertainty of cell division and highlights the significance of stochasticity for distinguishing between different modes of stem cell division.