Single-cell analyses of tissue regeneration in two true jellyfish

Abstract The phylum Cnidaria is the outgroup of Bilateria and includes sea anemones, corals, hydroids, and jellyfish. Cnidarians play crucial ecological roles in marine ecosystems, including the formation of highly diverse and productive coral reefs, and acting as important predator and prey species. They are also well known for their remarkable regeneration capacities. Here, we report single-cell RNA sequencing of bell tissue remodelling/regeneration after amputation in two species of scyphozoans or ‘true jellyfish’, the Asian moon jelly, Aurelia coerulea and the flame jellyfish, Rhopilema esculentum. We delineated 12 cell populations in Aurelia and Rhopilema and revealed their respective marker genes and enriched gene pathways. During this process, conserved transcription factor Otx, TFAP2A, Erg, NFIA and Wnt/β-catenin signalling pathway genes were identified. Additionally, we discovered two conserved, sequentially activated patterns, with putative proliferative cells, gastrodermal cells, neural cells, and secretory gland cells modulated in the first phase, followed by cnidocytes in the second phase. Further comparison among cnidarian genomes identified a suite of lineage-specific scyphozoan genes, a subset of which were frequently significantly expressed in cnidocytes in both jellyfish species. Using powerful single-cell RNA sequencing approaches, this study elucidates the evolution of lineage-specific genetic networks and biological processes in true jellyfish, which remain comparatively poorly studied, and in particular provides key insights into the molecular pathways underlying their remarkable regenerative capacity.