|Title||Molecular recording of mammalian embryogenesis.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Chan, MM, Smith, ZD, Grosswendt, S, Kretzmer, H, Norman, TM, Adamson, B, Jost, M, Quinn, JJ, Yang, D, Jones, MG, Khodaverdian, A, Yosef, N, Meissner, A, Weissman, JS|
|Date Published||2019 06|
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.