Single-cell transcriptome landscape of human fetal gonads defines somatic lineages specification and identifies GnRHR as a new Sertoli cell regulator

Gonad development is an exciting model to study cell fate commitment. A better understanding of sex determination requires the identification of all cell types involved and of their dynamic expression programs. Here we present a comprehensive analysis of approximately 128,000 single cells from human testes and ovaries between 5 and 12 postconceptional weeks. A focused analysis of somatic cells identified a population of bipotential progenitors derived from the coelomic epithelium of both male and female gonads and capable of committing to either a steroidogenic or a supporting fate. Moreover, we showed that early supporting cells, prior to differentiation into Sertoli or granulosa cells, also give rise to the rete testis/ovarii lineage. We found that the ovary retains the capacity to feed the supporting cell pool for an extended period of time, directly from the surface epithelium. Finally, we demonstrated that the GnRH signaling pathway regulates gene expression in human pre-Sertoli cells. Testicular mRNA profiles of human male fetal gonads at 5-6 PCW (postconceptional week) (n=10 individuals, 20 testes) exposed to DMSO ± Leuprolide (GnRHR agonist) during 24 hours hanging drop cultures were generated by Bulk RNA Barcoding and sequencing (BRB-seq). *************************************************************** Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access. ***************************************************************