Single-cell transcriptome landscape of developing fetal gonads defines somatic cell lineage specification in humans

Abstract

Gonad development is an exciting model to study cell fate commitment. However, the specification and differentiation of somatic cell lineages within the testis and the ovary are incompletely characterized, especially in humans. In fact, a better understanding of sex determination first requires the identification of all the cell types involved and of their dynamic expression programs. Here we present a comprehensive analysis of approximately 128,000 single cells collected from 33 fetal testes and ovaries between 5 and 12 postconceptional weeks. In particular, a focused analysis of somatic cells allowed us to identify a common 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 have shown that early supporting cells, prior to further differentiation into Sertoli or granulosa cells, also give rise to the rete testis/ovarii lineage. Finally, we found that the ovary retains the capacity to feed the supporting cell pool for an extended period of time, directly from the surface epithelial cells and, bypassing the bipotential progenitor step. Altogether, our results provide an unprecedented revisiting of the human gonadal sex determination process.

Rediscovering theRete Ovarii: a secreting auxiliary structure to the ovary

“…Recently, the IOR has gained attention as a newly described progenitor for supporting cells of the murine gonad (Mayère et al, 2022). Recent single cell transcriptomics studies have also identified cells of the RO within human fetal gonads (Lardenois et al, 2023; Taelman et al, 2022). We reported that the entire RO expresses high levels of PAX8, and chose to use this as a marker to visualize and characterize cells of the RO.…”