CRISPR-based lineage tracing of cells and tissues
Lineage tracing is a common method for the identification of all progeny originating from a single cell. While lineage tracing is widely used to study multicellular systems, it scales poorly to whole, complex tissues and organisms. The overall aim of this project is to employ CRISPR gene editing for the generation of diverse genetic barcodes in order to study lineage relationships in mouse cells and tissues. First, cultivated mouse embryonic stem cells will be used to investigate the relationship between barcode diversity and number of CRISPR target sites within a specific locus. Second, the barcoding system will be employed to decipher lineage relationships among neuronal and glial cells in the developing mouse brain using single cell RNA-seq. Our method will allow the generation of large-scale cell lineage maps in multicellular systems during development and disease.