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

• Published in: Nature communications Vol. 13; no. 1; p. 13
• Main Authors: Fabian, Peter, Tseng, Kuo-Chang, Thiruppathy, Mathi, Arata, Claire, Chen, Hung-Jhen, Smeeton, Joanna, Nelson, Nellie, Crump, J. Gage
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.01.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14/32; 45; 45/23; 45/91; 631/114/2114; 631/136/142; 631/136/2442; 631/1647/514/1949; 631/532/2063; 64/116; Accessibility; Animals; Cartilage; Cell Differentiation - physiology; Cell fate; Chromatin; Chromatin remodeling; Circuits; Danio rerio; Datasets; Diversification; Enhancers; Fibroblasts; GATA-3 protein; Gene expression; Gene Expression Regulation, Developmental; Genomics; Humanities and Social Sciences; Medicine; multidisciplinary; Neural crest; Neural Crest - cytology; Neural Crest - metabolism; Neural stem cells; Priming; Progenitor cells; Respiration; Science; Science (multidisciplinary); Single-Cell Analysis - methods; Skull; Skull - cytology; Stem cells; Stromal cells; Transcription factors; Transcriptome; Transcriptomes; Vertebrates; Zebrafish; Zebrafish - embryology; Zebrafish - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27594-w

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. Cranial neural crest generates a wide diversity of cell types. Here the authors perform single-cell profiling of neural crest to identify key enhancers and transcription factors for cell fate competency, thus revealing progressive acquisition of fate potential.