Cellular fate of intersex differentiation

Abstract

Infertile ovotestis (mixture of ovary and testis) often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains largely unknown. Here, we report the first comprehensive single-cell developmental atlas of the model ovotestis. We provide an overview of cell identities and a roadmap of germline, niche, and stem cell development in ovotestis by cell lineage reconstruction and a uniform manifold approximation and projection. We identify common progenitors of germline stem cells with two states, which reveal their bipotential nature to differentiate into both spermatogonial stem cells and female germline stem cells. Moreover, we found that ovotestis infertility was caused by degradation of female germline cells via liquid–liquid phase separation of the proteasomes in the nucleus, and impaired histone-to-protamine replacement in spermatid differentiation. Notably, signaling pathways in gonadal niche cells and their interaction with germlines synergistically determined distinct cell fate of both male and female germlines. Overall, we reveal a cellular fate map of germline and niche cell development that shapes cell differentiation direction of ovotestis, and provide novel insights into ovotestis development.

Isolation and Characterization of Germline Stem Cells in Protogynous Hermaphroditic Monopterus albus

“…Interestingly, we found that two morphologically distinct types of cells similar to fGSCs and SSCs were observed when the GSCs from the ovotestis were cultured. This observation was in line with the recent report showing that common progenitors exist in the intersex gonad [ 17 ]. Based on the single cell RNA-sequencing data, five different subtypes of germline stem cells were identified in ovotestis of M. albus : two common progenitor cell types, early spermatogonia, late spermatogonia, and fGSCs.…”

“…Inhibition of BMP signaling results in the premature formation of GSCs [ 50 ]. BMP signaling pathway genes bmp4 , smad7 , and Id1 are abundantly expressed in the Sertoli cells of M. albus , suggesting that somatic-tissue-derived BMP signaling is important for the maintenance of GSCs [ 17 ]. Thus, our data suggested that Wnt and Bmp signaling pathways may play important roles in the maintenance or development of GSCs, which provides key cues for optimizing our GSC medium.…”

“…This has been a bottleneck for swamp eel aquaculture. A recent study has shown that both female and male GSCs exist in the ovotestis of swamp eels [ 17 ]. Unfortunately, few studies have focused on the isolation and characterization of GSCs from M. albus .…”

A single‐cell transcriptomic atlas characterizes cell types and their molecular features in yak ovarian cortex

“…Single-cell RNA-sequencing technology has been applied to reveal cellular signatures of ovarian tissue of a few species. So far, the comprehensive ovarian cell atlases were built for humans, 20,21 monkeys, 22,23 drosophilas, [24][25][26] zebrafish, 27 seabass, 28 and finless eel 29 by scRNA-seq. Specific gene signatures of oocyte and granulosa cells were identified at different developmental stages that might reflect both oocyte competency and ovarian reserve in adult human ovaries.…”

Gonadal and cellular dynamics during protogynous sex change in the harlequin sandsmelt Parapercis pulchella

“…Our data reveal that oocytes are lost via apoptotic cell death during sex change. Histological observations showed that oocytes were decreased in number at the late transition stage (Figure 2e) and these oocytes disappeared in male testes, although a few remaining oocytes were observed in some testes, indicating that oocytes degenerated (Nozu et al, 2013;Wang et al, 2021), indicating that this process is common in protogynous species.…”