Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development

Authors

• EA Kohut
• SA Graff
• SH Wakelin
• M Arhin
• G Bhagavatheeshwaran
• JD Heiss

Abstract

During development, animals generate distinct cell populations with specific identities, functions, and morphologies. To profile the molecular cell types during vertebrate development, we mapped transcriptionally distinct populations across 489,686 cells from 62 stages during wild-type zebrafish embryogenesis and early larval development (3–120 hours post-fertilization). By analyzing these data together and per tissue, we generated a detailed catalog of >300 cell states in zebrafish development and characterized the developmental trajectory of transcriptional changes that occur during the differentiation of several cell types. Cross-tissue comparisons revealed the limited catalog of gene expression programs reused across multiple tissues and their cell-type-specific adaptations. Focused analyses of non-skeletal muscle and the endoderm identified transcriptional profiles of understudied cell types and subpopulations, including the pneumatic duct, individual intestinal smooth muscle layers, spatially distinct pericyte populations and homologs of recently discovered human best4+ enterocytes that are potentially linked to human disease. Their developmental origins and specification programs remain unexplored, so we used trajectory analysis to identify the cascade of gene expression events leading to these cells and predict candidate regulators that govern their specification. To enable additional discoveries, we have made this comprehensive transcriptional atlas of early zebrafish development available through our website, Daniocell. Funding: NIH Intramural ZIAHD008997 to JAF.

Scientific Focus Area: Developmental Biology

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