Molecular recording of mammalian embryogenesis.

TitleMolecular recording of mammalian embryogenesis.
Publication TypeJournal Article
Year of Publication2019
AuthorsChan, 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
JournalNature
Volume570
Issue7759
Pagination77-82
Date Published2019 06
ISSN1476-4687
KeywordsAnimals, Cell Differentiation, Cell Lineage, Embryo, Mammalian, Embryonic Development, Embryonic Stem Cells, Endoderm, Female, Fertilization, Gastrulation, Gene Expression Regulation, Developmental, Male, Mice, Organ Specificity, Phenotype, Sequence Analysis, RNA, Single-Cell Analysis
Abstract

<p>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.</p>

DOI10.1038/s41586-019-1184-5
Alternate JournalNature
PubMed ID31086336
PubMed Central IDPMC7229772
Grant ListT32 HG000047 / HG / NHGRI NIH HHS / United States
F32 GM116331 / GM / NIGMS NIH HHS / United States
RM1 HG009490 / HG / NHGRI NIH HHS / United States
R01 DA036858 / DA / NIDA NIH HHS / United States
R01 HD078679 / HD / NICHD NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
F32 GM125247 / GM / NIGMS NIH HHS / United States