Molecular recording of mammalian embryogenesis. Author Michelle Chan, Zachary Smith, Stefanie Grosswendt, Helene Kretzmer, Thomas Norman, Britt Adamson, Marco Jost, Jeffrey Quinn, Dian Yang, Matthew Jones, Alex Khodaverdian, Nir Yosef, Alexander Meissner, Jonathan Weissman Publication Year 2019 Type Journal Article Abstract 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. Keywords Animals, Mice, Sequence Analysis, RNA, Phenotype, Female, Male, Embryo, Mammalian, Embryonic Development, Gene Expression Regulation, Developmental, Fertilization, Single-Cell Analysis, Cell Differentiation, Cell Lineage, Organ Specificity, Gastrulation, Endoderm, Embryonic Stem Cells Journal Nature Volume 570 Issue 7759 Pages 77-82 Date Published 2019 Jun ISSN Number 1476-4687 DOI 10.1038/s41586-019-1184-5 Alternate Journal Nature PMCID PMC7229772 PMID 31086336 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML