Soma-germline communication drives sex maintenance in the Drosophila testis

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外文摘要：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(chinmoST)mutant Drosophila testis phenotype as a valuable model for investigating the mechanisms underlying sex maintenance.In chinmoST 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 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 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.

外文关键词：

Drosophila testissomatic stem cell sex conversionsingle-cell sequencingsoma-germline communicationinsulin signaling

作者：

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

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作者单位：

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

State Key Laboratory of Biocontrol,School of Life Sciences,Sun Yat-sen University,Guangzhou 510275,China

Department of Cell Biology,Johns Hopkins University School of Medicine,Baltimore,MD 21205,USA

基金：

National Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaGuangdong Basic and Applied Basic Research FoundationGuangdong Basic and Applied Basic Research FoundationGuangdong Provincial Key Laboratory of Synthetic GenomicsShenzhen Key Laboratory of Synthetic GenomicsShenzhen Institute of Synthetic Biology Scientific Research ProgramShenzhen Institute of Synthetic Biology Scientific Research ProgramStrategic Priority Research Program of the Chinese Academy of SciencesNational Institutes of HealthGuangzhou Key Research and Development Program

项目编号：

2022YFA0912900320708703207064432293190322931912021A15150107582024A15150112852023B1212060054ZDSYS201802061806209ZTXM20200008DWKF20210003XDB0480000R35GM1366652023B03J1347

出版年：

2024

DOI：

10.1093/nsr/nwae215

国家科学评论(英文版)

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ISSN：

年,卷(期)：2024.11(8)