Neoblast-like Stem Cells of <i>Fasciola hepatica</i>
Bibliographic record
Abstract
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 putative novel targets due to their role in development and homeostasis, including at 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, differentiation, and are sensitive to ionising radiation - all attributes of neoblasts in other flatworms. Changes in cell proliferation were also noted during the early stages of in vitro juvenile growth/development (around four to seven days post excystment), which coincided with a marked reduction in the nuclear area of proliferating cells. 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 homologues associated with neoblast-like cells in Schistosoma mansoni . Finally, RNA interference mediated knockdown of histone h2b (a marker of proliferating cells), ablated neoblast-like cells and impaired worm development in vitro . In summary, this work demonstrates that the proliferating cells of F. hepatica are equivalent to neoblasts of other flatworm species and demonstrate that they may serve as attractive targets for novel anthelmintics. Author Summary Liver fluke are parasitic worms that infect both livestock and humans worldwide, threatening food security and human health. Treatments against this disease-causing parasite are limited, and growing resistance to drugs is undermining the effectiveness of control strategies. Since drugs represent the only viable control option, it is crucial that new drugs are discovered through the identification and validation of new drug targets. Stem cells play important roles in the normal growth and repair processes of many organisms, but when these cells become dysregulated through mutation, they can drive the development of cancers. Stem cells of liver fluke may be attractive novel drug targets as disruption would affect worm survival and/or development within their host. In this research we describe the characteristics of liver fluke stem cells, such as their sensitivity to radiation and their ability to develop into new cell types (key stem cell features). We used radiation in combination with RNA sequencing to identify genes associated with the liver fluke stem cells. Finally, we used reverse genetics to reduce the expression of a gene associated with stem cells, which led to the loss of stem cells and reduced worm growth/development. These data provide evidence to support the exploitation of stem cells as a source of novel drug targets for liver fluke control.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".