Monitoring gonadal somatic cell differentiation during sex determination using single-cell RNA sequencing

Abstract

Mammalian sex determination is a particularly interesting model to study cell fate decision. Depending on the genetic sex, the common gonadal primordium is able to differentiate as two different organs, the testis and the ovary. This PhD project aimed to dissect with single-cell RNA-sequencing the process of sex determination in mouse by characterising the transcriptomic changes occurring in the different somatic cell lineages from the bipotential state to advanced developing testes and ovaries. For this purpose, we proceeded to single-cell RNA sequencing of the gonadal somatic cells (NR5A1 expressing cells) from XX and XY mice at key stages of the gonad development. With cell lineage predictive algorithms and pseudotime ordering, we were able to reconstruct the chronology of events driving testis and ovary development, as well as sex fate decision in both supporting and steroidogenic cell lineages