Asymmetric division sustains stem cell heterogeneity in the Drosophila testicular niche

The stem cell niche provides a specialized microenvironment that supports stem cell self-renewal. Spatial constraints within the niche limit the number of resident stem cells, leading to competition for niche occupancy. Such competition can result in neutral drift, where one stem cell clone gradually dominates the pool. Theoretically, a high rate of asymmetric division is expected to mitigate this competition and preserve clonal heterogeneity, but its quantitative impact on clonal dynamics within an in vivo niche has not been defined. In this study, we use the Drosophila male germline stem cell (GSC) niche as a model to investigate how division modes, symmetric versus asymmetric divisions, shape dynamics of stem cell clones. Through a combination of lineage tracing and mathematical modeling, we show that stem cells compete via neutral competition, and an increased frequency of asymmetric division markedly delays clonal expansion, thereby maintaining stem cell diversity over time. We further found that under conditions of non-neutral competition, stem cells can actively change their rate of asymmetric division in response to variations in niche occupancy. These findings highlight the essential role of asymmetric division in preserving stem cell heterogeneity. This principle may extend across diverse stem cell systems.