Zebrahub-Multiome: Uncovering Gene Regulatory Network Dynamics During Zebrafish Embryogenesis

During embryonic development, gene regulatory networks (GRNs) drive molecular differentiation of cell types. However, the temporal dynamics of these networks remain poorly understood. Here, we present Zebrahub-Multiome, a comprehensive, time-resolved atlas of zebrafish embryogenesis, integrating single-cell chromatin accessibility (scATAC-seq) and gene expression (scRNA-seq) from over 94,000 cells sampled across six key developmental stages (10 to 24 hours post-fertilization). Our analysis reveals early-stage GRNs shared across multiple lineages, followed by the emergence of lineage-specific regulatory programs during later stages. We also observe a shift in transcription factor (TF) influence from broad, multi-lineage roles in early development to more specialized, cell-type-specific functions as development progresses. Using in silico genetic perturbations, we highlight the dynamic role of TFs in driving cell fate decisions, emphasizing the gradual specialization of regulatory circuits. All data and analyses are made accessible through an interactive web portal, enabling users to explore zebrafish gene regulatory dynamics across time and cell types. This resource provides a foundation for hypothesis generation and deeper insights into vertebrate development.