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Spatial transcriptomics of a parasitic flatworm provides a molecular map of drug targets and drug resistance genes

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  • Svenja Gramberg

    (Justus Liebig University Giessen)

  • Oliver Puckelwaldt

    (Justus Liebig University Giessen)

  • Tobias Schmitt

    (Justus Liebig University Giessen)

  • Zhigang Lu

    (University of Hohenheim)

  • Simone Haeberlein

    (Justus Liebig University Giessen)

Abstract

The spatial organization of gene expression dictates tissue functions in multicellular parasites. Here, we present the spatial transcriptome of a parasitic flatworm, the common liver fluke Fasciola hepatica. We identify gene expression profiles and marker genes for eight distinct tissues and validate the latter by in situ hybridization. To demonstrate the power of our spatial atlas, we focus on genes with substantial medical importance, including vaccine candidates (Ly6 proteins) and drug resistance genes (glutathione S-transferases, ABC transporters). Several of these genes exhibit unique expression patterns, indicating tissue-specific biological functions. Notably, the prioritization of tegumental protein kinases identifies a PKCβ, for which small-molecule targeting causes parasite death. Our comprehensive gene expression map provides unprecedented molecular insights into the organ systems of this complex parasitic organism, serving as a valuable tool for both basic and applied research.

Suggested Citation

  • Svenja Gramberg & Oliver Puckelwaldt & Tobias Schmitt & Zhigang Lu & Simone Haeberlein, 2024. "Spatial transcriptomics of a parasitic flatworm provides a molecular map of drug targets and drug resistance genes," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53215-3
    DOI: 10.1038/s41467-024-53215-3
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    References listed on IDEAS

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    1. Carmen Lidia Diaz Soria & Jayhun Lee & Tracy Chong & Avril Coghlan & Alan Tracey & Matthew D. Young & Tallulah Andrews & Christopher Hall & Bee Ling Ng & Kate Rawlinson & Stephen R. Doyle & Steven Leo, 2020. "Single-cell atlas of the first intra-mammalian developmental stage of the human parasite Schistosoma mansoni," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    2. Hailey Sounart & Denis Voronin & Yuvarani Masarapu & Matthew Chung & Sami Saarenpää & Elodie Ghedin & Stefania Giacomello, 2023. "Miniature spatial transcriptomics for studying parasite-endosymbiont relationships at the micro scale," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
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