Hydra single-cell RNA-sequencing 2

Pacemaker neurons exert control over neuronal circuit function by their intrinsic ability togenerate rhythmic bursts of action potential. Recent work has identified rhythmic gutcontractions in human, mice and hydra to be dependent on both neurons and the residentmicrobiota. However, little is known about the evolutionary origin of these neurons andtheir interaction with microbes. In this study, we identified and functionally characterizedprototypical ANO/SCN/TRPM ion channel expressing pacemaker cells in the basalmetazoan Hydra by using a combination of single-cell transcriptomics,immunochemistry, and functional experiments. Unexpectedly, these prototypicalpacemaker neurons express a rich set of immune-related genes mediating their interactionwith the microbial environment. Functional experiments validated a model of theevolutionary emergence of pacemaker cells as neurons using components of innateimmunity to interact with the microbial environment and ion channels to generaterhythmic contractions.