Soma-germline communication drives sex maintenance in the Drosophila testis  

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

机构地区：[1]Shenzhen Key Laboratory of Synthetic Genomics,Guangdong Provincial Key Laboratory of Synthetic Genomics,Key Laboratory of Quantitative Synthetic Biology,Shenzhen Institute of Synthetic Biology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China [2]State Key Laboratory of Biocontrol,School of Life Sciences,Sun Yat-Sen University,Guangzhou 510275,China [3]Department of Cell Biology,Johns Hopkins University School of Medicine,Baltimore,MD21205,USA

出　　处：《National Science Review》2024年第8期92-107,共16页国家科学评论（英文版）

基　　金：supported by the National Key Research and Development Program of China(2022YFA0912900 to Q.Ma);the National Natural Science Foundation of China(32070870 to Q.Ma,32070644,32293190,and 32293191 to J.Xu);the Guangdong Basic and Applied Basic Research Foundation(2021A1515010758 to Q.Ma,2024A1515011285 to J.Xu);the Guangdong Provincial Key Laboratory of Synthetic Genomics(2023B1212060054 to Q.Ma);the Shenzhen Key Laboratory of Synthetic Genomics(ZDSYS201802061806209 to Q.Ma);the Shenzhen Institute of Synthetic Biology Scientific Research Program(ZTXM20200008 and DWKF20210003 to Q.Ma);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0480000 to Q.Ma);the National Institutes of Health(R35GM136665 to E.Matunis);the Guangzhou Key Research and Development Program(2023B03J1347 to J.Xu).

摘　　要：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(chinmo^(ST))mutant Drosophila testis phenotype as a valuable model for investigating the mechanisms underlying sex maintenance.In chinmo^(ST) testes,depletion of the Janus Kinase-Signal Transducer and Activator of Transcription downstream effector Chinmo from somatic cyst stem cells(CySCs)feminizes somatic cyst cells and arrests germline differentiation.Here,we use single-cell RNA sequencing to uncover chinmo^(ST)-specific cell populations and their transcriptomic changes during sex transformation.Comparative analysis of intercellular communication networks between wild-type and chinmo^(ST) testes revealed disruptions in several soma-germline signaling pathways in chinmo^(ST) testes.Notably,the insulin signaling pathway exhibited significant enhancement in germline stem cells(GSCs).Chinmo cleavage under targets and tagmentation(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.

关 键 词：Drosophila testis somatic stem cell sex conversion single-cell sequencing soma-germline communication insulin signaling 

分 类 号：Q96[生物学—昆虫学]