2024年6月22日，《国家科学评论》杂志在线发表了中国科学院深圳先进技术研究院马晴等研究人员的最新合作成果，该研究发现体细胞与生殖细胞的交流推动果蝇睾丸的性别维持。

研究人员表示，在成年性腺中，体细胞性特征的破坏会导致配子发生缺陷和不育。然而，体细胞信号调控生殖细胞以实现正常配子发生的潜在机制仍不清楚。在之前的研究中，研究人员引入了chinmo^{Sex Transformation}（chinmo^ST）突变果蝇睾丸表型作为研究性维持机制的宝贵模型。在chinmo^ST睾丸中，体细胞囊干细胞（CySC）中的JAK-STAT下游效应物Chinmo被耗尽，体细胞囊干细胞雌性化，生殖细胞分化停止。

研究人员利用单细胞RNA-seq发现了chinmo^ST特异性细胞群及其在性别转化过程中的转录组变化。对野生型睾丸和chinmo^ST睾丸细胞间通讯网络的比较分析表明，chinmo^ST睾丸的几种体细胞-生殖细胞信号通路发生了中断。

值得注意的是，胰岛素信号通路在生殖干细胞（GSC）中表现出显著增强。chinmo CUT&Tag分析显示，chinmo直接调控两个雄性性别决定因子：doublesex（dsx）和fruitless（fru），以及胰岛素信号通路的负调控因子——蜕皮激素诱导基因L2（ImpL2）。进一步的遗传操作证实，在chinmo睾丸中观察到的配子发生障碍部分是由胰岛素信号通路失调造成的。

总之，这些研究表明，体细胞性别维持通过chinmo介导的保守性别决定和胰岛素信号通路促进了正常的精子发生。该工作为体细胞干细胞性别维持和单细胞水平上的体细胞-生殖细胞交流的复杂机制提供了新的见解。此外，该发现强调了干细胞性别不稳定性作为导致睾丸肿瘤发生的新机制的潜在意义。

附：英文原文

Title: Soma-germline communication drives sex maintenance in the Drosophila testis

Author: Zhang, Rui, Shi, Peiyu, Xu, Shuyang, Ming, Zhe, Liu, Zicong, He, Yuanyuan, Dai, Junbiao, Matunis, Erika, Xu, Jin, Ma, Qing

Issue&Volume: 2024-06-22

Abstract: In adult gonads, disruption of somatic sexual identity leads to defective gametogenesis and infertility. However, the underlying mechanisms by which somatic signals regulate germline cells to achieve proper gametogenesis remain unclear. In our previous study, we introduced the chinmoSex Transformation(chinmoST) mutant Drosophila testis phenotype as a valuable model for investigating the mechanisms underlying sex maintenance. In chinmoST testes, depletion of the JAK-STAT downstream effector Chinmo from somatic cyst stem cells (CySCs) feminizes somatic cyst cells and arrests germline differentiation. Here, we use single-cell RNA-seq, to uncover chinmoST-specific cell populations and their transcriptomic changes during sex transformation. Comparative analysis of intercellular communication networks between wild-type and chinmoST testes revealed disruptions in several soma-germline signaling pathways in chinmoST testes. Notably, the Insulin signaling pathway exhibited significant enhancement in germline stem cells (GSCs). Chinmo CUT&Tag assay revealed that Chinmo directly regulates two male sex determination factors, doublesex (dsx) and fruitless (fru), as well as Ecdysone-inducible gene L2 (ImpL2), a negative regulator of the Insulin signaling pathway. Further genetic manipulations confirmed that the impaired gametogenesis observed in chinmoST testes was partly contributed by dysregulation of the Insulin signaling pathway. In summary, our study demonstrates that somatic sex maintenance promotes normal spermatogenesis through Chinmo-mediated conserved sex determination and the Insulin signaling pathway. Our work offers new insights into the complex mechanisms of somatic stem cell sex maintenance and soma-germline communication at the single-cell level. Additionally, our discoveries highlight the potential significance of stem cell sex instability as a novel mechanism contributing to testicular tumorigenesis.

DOI: 10.1093/nsr/nwae215

Source: https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwae215/7697574searchresult=1