RT Journal Article
SR Electronic
T1 Molecular recording of mammalian embryogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 384925
DO 10.1101/384925
A1 Michelle M. Chan
A1 Zachary D. Smith
A1 Stefanie Grosswendt
A1 Helene Kretzmer
A1 Thomas Norman
A1 Britt Adamson
A1 Marco Jost
A1 Jeffrey J. Quinn
A1 Dian Yang
A1 Alexander Meissner
A1 Jonathan S. Weissman
YR 2018
UL http://biorxiv.org/content/early/2018/08/03/384925.abstract
AB Understanding the emergence of complex multicellular organisms from single totipotent cells, or ontogenesis, represents a foundational question in biology. The study of mammalian development is particularly challenging due to the difficulty of monitoring embryos in utero, the variability of progenitor field sizes, and the indeterminate relationship between the generation of uncommitted progenitors and their progression to subsequent stages. Here, we present a flexible, high information, multi-channel molecular recorder with a single cell (sc) readout and apply it as an evolving lineage tracer to define a mouse cell fate map from fertilization through gastrulation. By combining lineage information with scRNA-seq profiles, we recapitulate canonical developmental relationships between different tissue types and reveal an unexpected transcriptional convergence of endodermal cells from extra-embryonic and embryonic origins, illustrating how lineage information complements scRNA-seq to define cell types. Finally, we apply our cell fate map to estimate the number of embryonic progenitor cells and the degree of asymmetric partitioning within the pluripotent epiblast during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems to facilitate a quantitative framework for describing developmental processes.