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

Peter Fabian, Kuo-Chang Tseng, Mathi Thiruppathy, Claire Arata, Hung-Jhen Chen, Joanna Smeeton, Nellie Nelson and J. Gage Crump ()
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Peter Fabian: University of Southern California Keck School of Medicine
Kuo-Chang Tseng: University of Southern California Keck School of Medicine
Mathi Thiruppathy: University of Southern California Keck School of Medicine
Claire Arata: University of Southern California Keck School of Medicine
Hung-Jhen Chen: University of Southern California Keck School of Medicine
Joanna Smeeton: University of Southern California Keck School of Medicine
Nellie Nelson: University of Southern California Keck School of Medicine
J. Gage Crump: University of Southern California Keck School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-021-27594-w

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