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Molecular recording of mammalian embryogenesis

Item Type:Article
Title:Molecular recording of mammalian embryogenesis
Creators Name:Chan, M.M. and Smith, Z.D. and Grosswendt, S. and Kretzmer, H. and Norman, T.M. and Adamson, B. and Jost, M. and Quinn, J.J. and Yang, D. and Jones, M.G. and Khodaverdian, A. and Yosef, N. and Meissner, A. and Weissman, J.S.
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:Cell Differentiation, Cell Lineage, Developmental Gene Expression Regulation, Embryonic Development, Embryonic Stem Cells, Endoderm, Fertilization, Gastrulation, Mammalian Embryo, Organ Specificity, Phenotype, RNA Sequence Analysis, Single-Cell Analysis, Animals, Mice
Publisher:Nature Publishing Group
Page Range:77-82
Date:6 June 2019
Official Publication:https://doi.org/10.1038/s41586-019-1184-5
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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