A First Cell Atlas of Fasciola hepatica

• Applicant: Dr. Simone Häberlein
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Veterinary Medical Science
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 444929758

The liver fluke Fasciola hepatica is a parasitic flatworm causing disease in humans and animals, and huge economic losses in livestock worldwide. Next to its medical importance, the liver fluke also owns a fascinating biology: when entering the host, it undergoes amazing developmental adaptions to its new environment leading to substantial growth. The hypothesis is that stem cells may play essential roles being key for the fluke development. Also, the fluke intestine is of interest as metabolically active tissue essential for fluke development. If damaged, this will cause the death of the parasite. To date, no cell- or organ-specific transcriptome data are available for F. hepatica. The project will establish transcriptomic datasets of three different developmental, intramammalian stages of F. hepatica in a spatial and single cell resolution by applying the cutting-edge techniques Spatial Transcriptomics and 10x Single-cell RNAseq. With this whole-organism cell atlas, we will (1) determine global changes of cell-specific expression patterns during fluke development, (2) identify stem cell-specific genes defining subtypes, and visualize their tissue distribution, (3) bioinformatically predict differentiation paths from stem cells to (intestinal) cell lineages to create a lineage tree of F. hepatica, and (4) analyze organ-specific gene expression with a focus on intestinal transcription factors. With post-genomic tools such as RNAi, the role of selected genes in fluke development will be studied. Spatial transcriptomics will be applied for the first time in helminth research allowing unprecedented insights into tissue- and cell type-specific gene expression of parasitic flatworms. The data will help understanding fluke development and identifying target genes as well as their tissue localization. Both may also be helpful in identifying novel targets for drug discovery, which has become important against the background of increasing resistance against commonly used drugs.

• DFG Programme: Research Grants