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Harvesting the power of a new model organism: stem cells, regeneration and ageing in Macrostomum lignano

Final Report Summary - MACMODEL (Harvesting the power of a new model organism: stem cells, regeneration and ageing in Macrostomum lignano)

This project significantly advanced a flatworm Macrostomum lignano as a novel powerful model organism to study mechanisms of regeneration, stem cell regulation and ageing. The project had two components: the development of genomic tools and resources for the flatworm M. lignano, and characterization of molecular mechanisms behind regeneration and ageing in this animal. First, we have generated a high quality annotated M. lignano transcriptome and genome assemblies, which are essential genomic resources for a model organism. Second, we developed a robust transgenesis method for M. lignano and generated multiple stable transgenic lines with tissue-specific expression patterns of the reporter transgenes, demonstrating for the first time that transgenesis can be routinely performed in flatworms. Third, we characterized gene expression in proliferating cells of the animal, established transcriptional signatures of somatic stem cells (neoblasts) and germline cells, and identified several novel genes essential for stem cell function. Fourth, we demonstrated that the investigation of flatworm-specific genes can yield valuable insights into flatworm biology. Finally, we studied how regeneration affects ageing in M. lignano and how expression of genes changes with age in this animal. In contrast to a previously proposed hypothesis that regeneration can lead to rejuvenation, we found that in M. lignano repeated regeneration does not result in rejuvenation or life extension. Instead, we discovered that the animals live substantially longer than previously appreciated and that this extended lifespan is accompanied by gene expression changes that make the animal resilient to ageing. It appeared that the animals might live very long because they actively regulate the so-called “biological quality” genes that help offsetting the effects of aging.
The generated high-quality genome assembly, the developed transgenesis method, the established transcriptional signatures of the proliferation cells and the discovered resilience to ageing in M. lignano lay solid foundation for further research in this novel powerful model organism.