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dc.contributor.authorTaxiarchi, Chrysanthien
dc.contributor.authorKranjc, Naceen
dc.contributor.authorKriezis, Antoniosen
dc.contributor.authorKyrou, Kyrosen
dc.contributor.authorBernardini, Federicaen
dc.contributor.authorRussell, Steveen
dc.contributor.authorNolan, Tonyen
dc.contributor.authorCrisanti, Andreaen
dc.contributor.authorGalizi, Robertoen
dc.date.accessioned2019-11-13T00:30:18Z
dc.date.available2019-11-13T00:30:18Z
dc.identifier.issn2045-2322
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/298851
dc.description.abstractAlthough of high priority for the development of genetic tools to control malaria-transmitting mosquitoes, only a few germline-specific regulatory regions have been characterised to date and the presence of global regulatory mechanisms, such as dosage compensation and meiotic sex chromosome inactivation (MSCI), are mostly assumed from transcriptomic analyses of reproductive tissues or whole gonads. In such studies, samples include a significant portion of somatic tissues inevitably complicating the reconstruction of a defined transcriptional map of gametogenesis. By exploiting recent advances in transgenic technologies and gene editing tools, combined with fluorescence-activated cell sorting and RNA sequencing, we have separated four distinct cell lineages from the Anopheles gambiae male gonads: premeiotic, meiotic (primary and secondary spermatocytes) and postmeiotic. By comparing the overall expression levels of X-linked and autosomal genes across the four populations, we revealed a striking transcriptional repression of the X chromosome coincident with the meiotic phase, classifiable as MSCI, and highlighted genes that may evade silencing. In addition, chromosome-wide median expression ratios of the premeiotic population confirmed the absence of dosage compensation in the male germline. Applying differential expression analysis, we highlighted genes and transcript isoforms enriched at specific timepoints and reconstructed the expression dynamics of the main biological processes regulating the key stages of sperm development and maturation. We generated the first transcriptomic atlas of A. gambiae spermatogenesis that will expand the available toolbox for the genetic engineering of vector control technologies. We also describe an innovative and multidimensional approach to isolate specific cell lineages that can be used for the targeted analysis of other A. gambiae organs or transferred to other medically relevant species and model organisms.
dc.description.sponsorshipThis study was supported by a grant from the Foundation for the National Institutes of Health through the Vector-Based Control of Transmission: Discovery Research (VCTR) program of the Grand Challenges in Global Health initiative of the Bill & Melinda Gates Foundation.
dc.languageengen
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleHigh-resolution transcriptional profiling of Anopheles gambiae spermatogenesis reveals mechanisms of sex chromosome regulation.en
dc.typeArticle
prism.number14841en
prism.publicationNameScientific Reportsen
prism.volume9en
dc.identifier.doi10.17863/CAM.45906
dcterms.dateAccepted2019-09-25en
rioxxterms.versionofrecord10.1038/s41598-019-51181-1en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-09-25en
dc.contributor.orcidRussell, Steve [0000-0003-0546-3031]
dc.identifier.eissn2045-2322
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBill & Melinda Gates Foundation (via Foundation for the National Institutes of Health (FNIH)) (via Imperial College London) (LBEE P41643)
cam.issuedOnline2019-10-16en


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International