Lifelong single-cell profiling of cranial neural crest diversification in zebrafish.

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Public Summary:
The study explores how cranial neural crest cells, responsible for various head tissues, develop diverse abilities. By analyzing zebrafish, they found that these cells gradually gain access to specific DNA regions, allowing them to become different specialized cell types over time. These include cells for skeletal structures, regeneration, and respiration in the gills. Surprisingly, the cells' potential for various lineages is not predetermined but acquired progressively through changes in their DNA accessibility. This research provides insights into the development of head tissues and catalogs the cells involved.
Scientific Abstract:
The cranial neural crest generates a huge diversity of derivatives, including the bulk of connective and skeletal tissues of the vertebrate head. How neural crest cells acquire such extraordinary lineage potential remains unresolved. By integrating single-cell transcriptome and chromatin accessibility profiles of cranial neural crest-derived cells across the zebrafish lifetime, we observe progressive and region-specific establishment of enhancer accessibility for distinct fates. Neural crest-derived cells rapidly diversify into specialized progenitors, including multipotent skeletal progenitors, stromal cells with a regenerative signature, fibroblasts with a unique metabolic signature linked to skeletal integrity, and gill-specific progenitors generating cell types for respiration. By retrogradely mapping the emergence of lineage-specific chromatin accessibility, we identify a wealth of candidate lineage-priming factors, including a Gata3 regulatory circuit for respiratory cell fates. Rather than multilineage potential being established during cranial neural crest specification, our findings support progressive and region-specific chromatin remodeling underlying acquisition of diverse potential.