MAMMALIAN SYNTHETIC RECORDER

Reconstructing mammalian development

The genome of each multicellular organism contains the instructional complement for launching and executing a highly reproducible program of development. In principle, the developmental program orchestrated by a genome can be comprehensively described, as illustrated by Sulston and colleagues’ heroic reconstruction of the complete embryonic lineage of the roundworm C. elegans. However, nearly forty years later, C. elegans remains the only organism for which such a complete description of cell lineage has been realized. Several years ago, we demonstrated the concept of using CRISPR/Cas9-mediated genome editing for organism-scale cell lineage recording during in vivo development (GESTALT; McKenna et al. 2016). However, there are numerous technical and practical challenges on the path between this early proof-of-concept and a Sulston-like map of early mouse development. In collaboration with the SyRGe, we propose to synthesize and deploy the Mammalian Synthetic Recorder Locus v1.0, which will record both lineage histories and other aspects of cell state in a way that addresses many of these challenges, and at a scale commensurate with the complexity of mammalian embryogenesis.

Working on this project:

IN COLLABORATION WITH:

Sudarshan Pinglay, PhD, University of Washington

Jay Shendure, MD, PhD, University of Washington

Flo Chardon, University of Washington

Will (Wei) Chen, University of Washington

Junhong Choi, University of Washington

Troy McDiarmid, University of Washington