GSE119045
Apoptosis in the fetal testis eliminates developmentally defective germ cell clones
Mammalian egg and sperm are produced by germ cells (GCs) that develop in the embryo long before reproductive maturity. Many GCs that begin this process do not contribute their genes to the next generation, although it remains unclear what determines GC fitness. Here, we examined how the composition of GCs in the fetal testis is affected by scheduled apoptosis as GCs transition between proliferation to sex differentiation. Using multicolored-lineage tracing, we find that apoptosis affects clonally-related GCs, suggesting that this fate decision occurs autonomously based on shared intrinsic properties. Single cell RNA-sequencing reveals extensive heterogeneity among GCs and identifies a Trp53-high subpopulation with elevated apoptotic susceptibility and diminished differentiation. By contrast, the most differentiated subpopulation is depleted for pro-apoptotic transcripts. These results indicate that cell-heritable differences in sex-differentiation segregate GCs into subpopulations with distinct fitness. The reciprocal relationship between sex-differentiation and apoptosis coordinates the removal of developmentally incompetent cells to improve male GC quality. Overall design: Single cell RNA sequencing of E12.5 and E13.5 male germ cells.