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

Nat Commun. 2022 Jan 10;13(1):13. doi: 10.1038/s41467-021-27594-w.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Chromatin
  • Gene Expression Regulation, Developmental
  • Neural Crest* / cytology
  • Neural Crest* / metabolism
  • Single-Cell Analysis* / methods
  • Skull / cytology
  • Transcriptome
  • Zebrafish / embryology*
  • Zebrafish / metabolism

Substances

  • Chromatin