A single-celled totipotent zygote produces a multitude of different cell types, where cells undergo zygotic genome activation, lineage selection and refinement, and eventually the engagement of differentiation programmes. However, the cell-to-cell genome regulation that drives these events is poorly understood. Combining single-cell profiling with the known lineage of C. elegans makes it feasible to determine the locus-specific regulation of chromatin, gene expression, and nuclear organisation in every single cell from the zygote to the differentiated state. We are using single cell profiling and super-resolution microscopy to determine the genome regulatory changes from mother to daughter cells that drive developmental decisions and their expression across complete developmental trajectories.