PROJECT ID: GSE153961


Data source GEO: GSE153961
Description Ovotestis often occurs in intersex individuals under certain pathological and physiological conditions. However, how ovotestis is formed remains unknown. Here, we report the first comprehensive single-cell developmental atlas of the model fish ovotestis. We provide an overview of ovotestis 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 developmental defects in oogenesis owing to dynamic autophagic degradation in female germline cells, and in spermatogenesis due to deficiency of histone-to-protamine replacement in spermatid differentiation. Notably, signaling pathways in gonadal niche cells and their interaction with germline cells synergistically determined cell fates of both male and female germlines in ovotestis. Overall, we reveal a cellular fate map of germline and niche cell development that shapes cell differentiation directions of ovotestis, and provide novel insights into ovotestis development.
Key word infertile ovotestis; Monopterus albus; spermatogonial stem cells; female germline stem cells
Publication Wang X, Lai F, Shang D, Cheng Y et al. Cellular fate of intersex differentiation. Cell Death Dis 2021 Apr 12;12(4):388. PMID: 33846307
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.


Dataset Information


Dataset ID Species Tissue / Organ Experiment type Sample Source dataset ID
1. GSE153961 (intersex) Monopterus albus gonad baseline adult, untreatment GEO: GSM4661001

Clustering Result


Cluster Cell type Gene id (symbol) Marker class Evidence
1 Early round spermatids spag6 (spag6) marker DOI:10.1038/s41419-021-03676-x
2 Zygotene primary spermatocytes meiob (meiob) marker DOI:10.1038/s41419-021-03676-x
3 Pachytene primary spermatocytes sycp2 (sycp2) marker DOI:10.1038/s41419-021-03676-x
4 Spermatogonia B cdca3 (cdca3) marker DOI:10.1038/s41419-021-03676-x
4 Spermatogonia B kmt5a (kmt5a) marker DOI:10.1016/j.ejcb.2018.12.002
4 Spermatogonia B kif20a (kif20a) marker DOI:10.1016/j.ejcb.2018.12.002
5 Germline stem cells nanos3 (nanos3) marker DOI:10.1016/j.cbpb.2019.06.002
5 Germline stem cells dnd1 (dnd1) marker DOI:10.1016/j.gene.2018.08.068
6 Metaphase,anaphase primary spermatocytes mlh3 (mlh3) marker DOI:10.1038/s41419-021-03676-x
7 Premeiotic S phase cells dnmt1 (dnmt1) marker DOI:10.1016/j.devcel.2010.09.010
8 Leptotene primary spermatocytes nasp (nasp) marker DOI:10.1038/s41419-021-03676-x
9 Secondary spermatocytes racgap1 (racgap1) marker DOI:10.1038/s41419-021-03676-x
10 Late round spermatids LOC109972762 (LOC109972762) marker DOI:10.1038/s41419-021-03676-x
11 Sertoli cells LOC109969035 (LOC109969035) marker DOI:10.1038/s41419-021-03676-x
11 Sertoli cells amh (amh) marker DOI:10.1038/s41419-021-03676-x
12 Leydig cells star (star) marker DOI:10.1038/s41419-021-03676-x
12 Leydig cells LOC109973668 (LOC109973668) marker DOI:10.1038/s41419-021-03676-x