Molecular recording of mammalian embryogenesis


  • M.M. Chan
  • Z.D. Smith
  • S. Grosswendt
  • H. Kretzmer
  • T.M. Norman
  • B. Adamson
  • M. Jost
  • J.J. Quinn
  • D. Yang
  • M.G. Jones
  • A. Khodaverdian
  • N. Yosef
  • A. Meissner
  • J.S. Weissman


  • Nature


  • Nature 570 (7759): 77-82


  • Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps 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, which will facilitate the construction of a quantitative framework for understanding developmental processes.