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Molecular recording of mammalian embryogenesis

Item Type:Article
Title:Molecular recording of mammalian embryogenesis
Creators Name:Chan, M.M., Smith, Z.D., Grosswendt, S., Kretzmer, H., Norman, T.M., Adamson, B., Jost, M., Quinn, J.J., Yang, D., Jones, M.G., Khodaverdian, A., Yosef, N., 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
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group
Volume:570
Number:7759
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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