TITLE: “Imaging-based genetic recording of developmental histories”
ABSTRACT: Systems-level understanding of cell fate decisions has been hampered by limitations of the existing methods to capture developmental history of the cells. Synthetic recording, which uses genome editing to create sequence diversity in genetic barcodes, is emerging as a promising approach for mapping cell lineage and molecular history. However, readout of the information stored in the barcodes by sequencing leads to loss of crucial information about the spatial context of the cells and their organization in the tissue. We have developed a system for scalable in situ readout of DNA barcodes and single nucleotide modifications in cells and tissue sections. Together with multiplexed in situ transcriptional profiling and CRISPR base editing, this method enables us to trace lineage of many cells in each individual embryo, reconstruct lineage trees, and even connect the gene expression and signaling history of the progenitors to their eventual fates. In this talk, I present our approach to imaging-based barcoding and discuss how this technology can be used to investigate elusive aspects of cell fate specification in the mammalian retina.