Kinetics of cell division in epidermal maintenance

TL;DR

This paper investigates how cell division and differentiation govern epidermal maintenance, using clonal fate data to infer underlying rules and explore early cancer development mechanisms in mouse skin.

Contribution

It introduces a method to infer cell division and differentiation rules from clone fate data and applies it to understand skin maintenance and early cancer stages.

Findings

Cells divide independently rather than synchronously.

Long-term and short-term clone fate data can estimate division and differentiation rates.

Clonal fate data may reveal early cancer onset mechanisms.

Abstract

The rules governing cell division and differentiation are central to understanding the mechanisms of development, aging and cancer. By utilising inducible genetic labelling, recent studies have shown that the clonal population in transgenic mouse epidermis can be tracked in vivo. Drawing on these results, we explain how clonal fate data may be used to infer the rules of cell division and differentiation underlying the maintenance of adult murine tail-skin. We show that the rates of cell division and differentiation may be evaluated by considering the long-time and short-time clone fate data, and that the data is consistent with cells dividing independently rather than synchronously. Motivated by these findings, we consider a mechanism for cancer onset based closely on the model for normal adult skin. By analysing the expected changes to clonal fate in cancer emerging from a simple two-stage mutation, we propose that clonal fate data may provide a novel method for studying the earliest stages of the disease.