Molecular recording of mammalian embryogenesis

Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. In mammals, this field is particularly challenging due to the indeterminate relationship between self-renewal and differentiation, variation of progenitor field sizes, and internal gestation. Here, we present a flexible, high information, multi-channel molecular recorder with a single cell (sc) readout and apply it as an evolving lineage tracer to define a mouse cell fate map from fertilization through gastrulation. By combining lineage information with scRNA-seq profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells from extra-embryonic and embryonic origins. Finally, we apply our cell fate map to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems to facilitate a quantitative framework for understanding developmental processes.