Cell phylogeny records the parent-offspring relationships of individual cells. Combined with single-cell multi-omics, lineage mapping through genetically-engineered DNA barcodes enables the measurements of both phylogenetic tree and omics information for individual cells, thus providing important important insights into the developmental and disease processes. In the first part, I will introduce the application of a base editor-based lineage tracing technique to delineate the origin and evolution of early premalignant lesions in mouse model of colorectal cancers. Our systematic lineage mapping and quantitative inferences revealed a novel polyclonal-to-monoclonal transition during early colorectal tumorigenesis. In the second part, I will introduce a functional genomics approach to understanding 3D genome organization through systematic perturbation using synthetic transcription factors. This approach allows the establishment of causal relationships between transcription factor activation and 3D genome organization.

lineage tracing,functional genomics,somatic evolution,single-cell genomics