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

Abstract

AbstractThe spatial organization of gene expression dictates tissue functions in multicellular parasites. Here, we present the first spatial transcriptome of a parasitic flatworm, the common liver flukeFasciola hepatica.We identified gene expression profiles and marker genes for eight distinct tissues and validated the latter byin situhybridization. To demonstrate the power of our spatial atlas, we focused on genes with substantial medical importance, including vaccine candidates (Ly6 proteins), drug targets (β-tubulins, protein kinases) and drug resistance genes (glutathione S-transferases, ABC transporters). Several of these genes exhibited unique expression patterns, indicating tissue-specific biological functions. Notably, the prioritization of tegumental protein kinases identified a PKCβ, for which small-molecule targeting caused 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.