Time-resolved single-cell Multiomic zebrafish atlas

During development, dynamic interplay between transcription factors, chromatin, and genes, termed gene regulatory network (GRN), shapes the cell fate determination along the developmental trajectory. Recent advances in joint measurement of chromatin accessibility and gene expression enabled the genome-wide identification of regulatory relationships. Here, we assess the dynamics of the gene regulatory network in zebrafish development using joint single-cell ATAC and single-cell RNA sequencing. We discovered some key regulatory modules that exhibit cell-type and time-dependent activity, suggesting that the role of transcription factors vary over cell type and timepoints. With time-resolved GRNs combined with linear modeling framework, we performed a systematic in silico knock-out simulation using CellOracle. This in silico knock-out simulation revealed that the role of transcription factors is shared between mesodermal and neuro-ectodermal lineages in the early timepoints, but later commit significantly to either lineages. Together, we provide a dataset and a framework to systematically dissect the role of transcription factors during the zebrafish embryonic development.