Cell cycle lengths of stem cells and their lineage from cellular demography

Abstract

AbstractAdult stem cells and their transit-amplifying (TA) progeny dynamically alter their proliferation rates to maintain tissue homeostasis. To test how the division rates of stem cell and TA cells affect tissue growth and differentiation, we developed a computation strategy which estimates the average cell cycle lengths/lifespans of germline stem cells (GSCs) and their TA progeny from cellular demography. Analysis of the wild-type data from Drosophila testis using this method indicated anomalous changes in lifespans during the germline transit-amplification with a nearly 1.3-fold increase after the first division and about a 2-fold decrease in the subsequent stage. Genetic perturbations altering the cell cycle rates of GSC and its immediate daughter, the gonialblast (GB), proportionately changed the rates of subsequent TA divisions. Notably, a nearly 2-fold increase or decrease in the total TA duration did not alter the induction of meiosis after four mitotic cycles. Altogether, these results suggest that the rates of GSC and GB divisions can adjust the rates of subsequent divisions and the onset of differentiation.Significance StatementDynamic regulation of the proliferation rate of stem cells and their transit-amplifying daughters maintains tissue homeostasis in different conditions such as tissue regeneration, aging, and hormonal imbalance. Previous studies suggested that a molecular clock in the stem cell progeny determines the timing of differentiation. This work shows that alterations of the rates of stem cell divisions, as well as that of its progeny, could override the differentiation clock in the Drosophila testis, and highlights a possible mechanism of fine-tuning the transit-amplification program under different conditions such as tissue damage, aging, and hormonal inputs. Also, the method developed for this study could be adapted to estimate lineage expansion plasticity from demographic changes in other systems.HighlightsDetermination of cellular lifespan during transit-amplification from demographyLifespans of Drosophila male germline cells changes anomalously during the TALifespan changes of germline stem cells readjust that of the progeny cellsAnomalous lifespan expansion midway through TA precedes the Bam onset