Molecular recording of mammalian embryogenesis

Michelle M. Chan, Zachary D. Smith, Stefanie Grosswendt, Helene Kretzmer, Thomas M. Norman, Britt Adamson, Marco Jost, Jeffrey J. Quinn, Dian Yang, Matthew G. Jones, Alex Khodaverdian, Nir Yosef, Alexander Meissner, Jonathan S. Weissman

Research output: Contribution to journalArticlepeer-review

196 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)77-82
Number of pages6
Issue number7759
StatePublished - Jun 6 2019

All Science Journal Classification (ASJC) codes

  • General


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