Speaker
Description
An active pool of spermatogonial stem cells (SSCs) maintain male fertility. The effects of aging on the SSC pool remains poorly understood. Here, we used in vivo CRISPR barcoding to label zebrafish SSCs to study how SSC clones contribute to sperm production. We sampled sperm from barcoded zebrafish every month over their entire fertile lifespan. Sequencing of these sperm samples suggests that only a fraction of embryonic germ cells ever participate in sperm production. Moreover, we find that the relative contributions of each clone shifts dramatically over time. To understand the basis of this temporal variation, we developed a mathematical model of stem cell clonal dynamics and serial sperm sampling. Our model demonstrates that most SSC clones show evidence of population drift and that the clonal dynamics we observe do not conform to a neutral model where clones have equal fitness and their dynamics are driven solely by random chance. While past literature argues that individual clones drift neutrally in the testis, our results suggest that clonal interactions across the entire organ are more complex. Overall, our findings reveal the in vivo consequences of SSC heterogeneity and provide new insight into the mechanisms linking genetic variation, aging, and evolutionary dynamics in the testis stem cell niche.
