Single-cell profiling of Anopheles gambiae spermatogenesis defines the onset of meiotic silencing and premeiotic overexpression of the X chromosome

Page, Nicole; Taxiarchi, Chrysanthi; Tonge, Daniel; Kuburic, Jasmina; Chesters, Emily; Kriezis, Antonios; Game, Laurence; Kyrou, Kyros; Game, Laurence; Nolan, Tony; Galizi, Roberto

Abstract

Understanding development and genetic regulation in the Anopheles gambiae germline is essential to engineer effective genetic control strategies targeting this malaria mosquito vector. These include targeting the germline to induce sterility or using regulatory sequences to drive transgene expression for applications such as gene drive. However, only very few germline-specific regulatory elements have been characterised with the majority showing leaky expression. This has been shown to considerably reduce the efficiency of current genetic control strategies, which rely on regulatory elements with more tightly restricted spatial and/or temporal expression. Meiotic silencing of the sex chromosomes limits the flexibility of transgene expression to develop effective sex-linked genetic control strategies. Here, we build on our previous study, dissecting gametogenesis into four distinct cell populations, using single-cell RNA sequencing to define eight distinct cell clusters and associated germline cell–types using available marker genes. We reveal overexpression of X-linked genes in a distinct cluster of pre-meiotic cells and document the onset of meiotic silencing of the X chromosome in a subcluster of cells in the latter stages of spermatogenesis. This study provides a comprehensive dataset, characterising the expression of distinct cell types through spermatogenesis and widening the toolkit for genetic control of malaria mosquitoes.

• Journal Article Type: Article
• Acceptance Date: Aug 7, 2023
• Online Publication Date: Aug 15, 2023
• Publication Date: Aug 15, 2023
• Deposit Date: Aug 16, 2023
• Journal: Communications Biology
• Print ISSN: 2399-3642
• Electronic ISSN: 2399-3642
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 1
• Article Number: 850
• DOI: https://doi.org/10.1038/s42003-023-05224-z
• Keywords: chromosome; cell profiling; sperm cells
• Publisher URL: https://www.nature.com/articles/s42003-023-05224-z
• Additional Information: This article is licensed under a Creative Commons; Attribution 4.0 International License, which permits use, sharing,; adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were mad