Neoblast-like stem cells of Fasciola hepatica

Paul McCusker*, Nathan G. Clarke, Erica Gardiner, Rebecca Armstrong, Erin M. McCammick, Paul McVeigh, Emily Robb, Duncan Wells, Madelyn Nowak-Roddy, Abdullah Albaqami, Angela Mousley, Jonathan A. Coulter, John Harrington, Nikki J. Marks, Aaron G. Maule*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

The common liver fluke, Fasciola hepatica, causes the disease fasciolosis, which results in considerable losses within the global agri-food industry. There is a shortfall in the drugs that are effective against both the adult and juvenile life stages within the mammalian host, such that new drug targets are needed. Over the last decade the stem cells of parasitic flatworms have emerged as reservoirs of novel putative targets due to their roles in development and homeostasis, including of host-parasite interfaces. Here, we investigate and characterise the proliferating cells that underpin development in F. hepatica. We provide evidence that these cells are capable of self-renewal, are capable of differentiation, and are sensitive to ionising radiation - all attributes of neoblasts in other flatworms. Furthermore, we generated transcriptomes from worms following irradiation-based ablation of neoblasts, identifying 124 significantly downregulated transcripts, including known stem cell markers such as fgfrA and plk1. Sixty-eight of these had homologs associated with neoblast-like cells in S. mansoni. Finally, RNA interference mediated knockdown of histone h2b (a marker of proliferating cells), ablated neoblasts and impaired worm development in vitro. In summary, this work demonstrates that the proliferating cells of F. hepatica are equivalent to the neoblasts of other flatworm species and demonstrate that they may serve as attractive targets for novel anthelmintics.

Original languageEnglish
Article numbere1011903
Number of pages23
JournalPLoS Pathogens
Volume20
Issue number5
DOIs
Publication statusPublished - 28 May 2024

Keywords

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Fasciola hepatica
  • Fascioliasis - parasitology
  • Stem Cells

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