Molecular recording of mammalian embryogenesis
Authors
- 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
Journal
- Nature
Citation
- Nature 570 (7759): 77-82
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.