Many flatworms can alternate between asexual and sexual reproduction. This is a powerful reproductive strategy enabling them to benefit from the features of the two reproductive modes, namely, rapid multiplication and genetic shuffling. The two reproductive modes are enabled by the presence of pluripotent adult stem cells (neoblasts), by generating any type of tissue in the asexual mode, and producing and maintaining germ cells in the sexual mode. In the current study, RNA sequencing (RNA-seq) was used to compare the transcriptomes of two phenotypes of the planarian Dugesia ryukyuensis : an asexual OH strain and an experimentally sexualized OH strain. Pathway enrichment analysis revealed striking differences in amino acid metabolism in the two worm types. Further, the analysis identified serotonin as a new bioactive substance that induced the planarian ovary de novo in a postembryonic manner. These findings suggest that different metabolic states and physiological conditions evoked by sex-inducing substances likely modulate stem cell behavior, depending on their different function in the asexual and sexual reproductive modes. The combination of RNA-seq and a feeding assay in D. ryukyuensis is a powerful tool for studying the alternation of reproductive modes, disentangling the relationship between gene expression and chemical signaling molecules.

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