A demographic model for estimating the inter-division lifespans of stem cells and the subsequent transit amplifying stages

Abstract

AbstractThe division rates of stem cells and their progeny shape the growth and maintenance of tissues. Here, we present a mathematical model that could estimate the stage-wise lifespans of germline stem cells (GSCs) and subsequent transit amplifying (TA) cells from their steady-state distribution in Drosophila testis. Analysis of the wild-type data using this model indicated that the inter-division lifespans of the first two TA cycles remain similar to that of the GSCs, and then reduce by nearly 2-folds for the third and fourth cycles. Also, loss of Cyclin E and Cdk1 functions in the early germline cells, which decreased the rates of GSC divisions, is suggested to extend the lifespans of GSCs and the TA stages without affecting subsequent differentiation. Similar perturbations at the 4 and 8-cell stages, however, arrested the mitoses at the 8-cell stage, and only the Cyclin E-deficient cells continued with premature meiosis. Together, these results suggest that regulation of the G1-S and G2-M transitions in the GSCs and the rapidly dividing TA stages differentially impacts the amplification of the germline pool and subsequent differentiation. The model also helped to quantify distinct influences of these cell cycle regulatory molecules in determining the lifespans at different TA stages.HighlightsA model for calculating the lifespans of transit amplifying stages from demography. Transit-amplifying divisions accelerate by nearly 2-folds after the second mitosis. Cyclin E and Cdk1 regulate the lifespans of GSCs and transit amplifying cells. The premature arrest of the final transit amplifying division induces meiosis.