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bioRxiv · 10.1101/2021.08.19.456710

Lifelong single-cell profiling of cranial neural crest diversification

Fabian, P.·Tseng, K.-C.·Thiruppathy, M.·Arata, C.·Chen, H.-J.·Smeeton, J.·Nelson, N.·Crump, J. G.
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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 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 an intrinsic property of cranial neural crest, our findings support progressive and region-specific chromatin remodeling underlying acquisition of diverse neural crest lineage potential. HighlightsO_LISingle-cell transcriptome and chromatin atlas of cranial neural crest C_LIO_LIProgressive emergence of region-specific cell fate competency C_LIO_LIChromatin accessibility mapping identifies candidate lineage regulators C_LIO_LIGata3 function linked to gill-specific respiratory program C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/456710v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@1c4ca91org.highwire.dtl.DTLVardef@cf0d10org.highwire.dtl.DTLVardef@162bfe9org.highwire.dtl.DTLVardef@2565fd_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Fabian, P., Tseng, K.-C., Thiruppathy, M., Arata, C., Chen, H.-J., Smeeton, J., Nelson, N., Crump, J. G.. 2021-08-19. Lifelong single-cell profiling of cranial neural crest diversification. https://doi.org/10.1101/2021.08.19.456710

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