Dissecting the 3D regulatory landscape of the developing cerebral cortex with single-cell epigenomics

Understanding how different epigenetic layers are coordinated to facilitate robust lineage decisions during development is one of the fundamental questions in regulatory genomics. Using single-cell epigenomics coupled with cell-type specific high-throughput mapping of enhancer activity, DNA methylation and the 3D genome landscape in vivo, we dissected how the epigenome is rewired during cortical development. We identified and functionally validated key transcription factors such as Neurog2 which underlie regulatory dynamics and coordinate rewiring across multiple epigenetic layers to ensure robust lineage specification. This work showcases the power of high-throughput integrative genomics to dissect the molecular rules of cell fate decisions in the brain and more broadly, how to apply them to evolution and disease.