Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Renmin Hospital of Wuhan University, Wuhan, China.
Cell Death Dis. 2021 Apr 12;12(4):388. doi: 10.1038/s41419-021-03676-x.
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.
不育的卵睾（卵巢和睾丸的混合物）常在某些病理和生理条件下的两性畸形个体中出现。然而，卵睾的形成方式在很大程度上仍是未知的。在这里，我们报告了首例模型卵睾的全面单细胞发育图谱。通过细胞谱系重建和一致流形逼近和投影，我们提供了卵睾中生殖细胞、巢区和干细胞发育的细胞身份概述和路线图。我们确定了具有两种状态的生殖干细胞的共同祖细胞，揭示了它们分化为精原干细胞和雌性生殖干细胞的双潜能性质。此外，我们发现卵睾不育是由于核内蛋白酶体通过液-液相分离导致雌性生殖细胞降解，以及在精细胞分化过程中组蛋白到鱼精蛋白的替代受损所致。值得注意的是，性腺巢区细胞中的信号通路及其与生殖细胞的相互作用协同决定了雄性和雌性生殖细胞的不同细胞命运。总体而言，我们揭示了生殖细胞和巢区细胞发育的细胞命运图谱，塑造了卵睾的细胞分化方向，并为卵睾发育提供了新的见解。
