Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq

The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism single-cell transcriptomics to map adult and larval cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal with complex tissue-level body-plan organization. We uncover eight broad cell classes in Nematostella, including neurons, cnidocytes, and digestive cells. Each class comprises different subtypes defined by the expression of multiple specific markers. In particular, we characterize a surprisingly diverse repertoire of neurons, which comparative analysis suggests are the result of lineage-specific diversification. By integrating transcription factor expression, chromatin profiling, and sequence motif analysis, we identify the regulatory codes that underlie Nematostella cell-specific expression. Our study reveals cnidarian cell type complexity and provides insights into the evolution of animal cell-specific genomic regulation. [Display omitted] •Integrative single-cell analysis of whole-organism cell type regulatory programs•Nematostella vectensis adult and larval cell atlas reveals high cell type diversity•Independent diversification of neuronal cell type repertoires in Cnidaria/Bilateria•Pre-bilaterian complex cis-regulatory landscapes linked to cell type specification An integrative whole-organism single-cell analysis in Nematostella vectensis reveals cnidarian cell type complexity and provides insights into the mechanisms of animal cell-specific genomic regulation and evolution.