Molecular recording of mammalian embryogenesis.
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IF: 69.504
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Cited by: 220
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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

Seurat
Gene Expression
Spatial Transcriptomics

MeSH terms

Animals
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

Authors

Chan, Michelle M
Smith, Zachary D
Grosswendt, Stefanie
Kretzmer, Helene
Norman, Thomas M
Adamson, Britt
Jost, Marco
Quinn, Jeffrey J
Yang, Dian
Jones, Matthew G
Khodaverdian, Alex
Yosef, Nir
Meissner, Alexander
Weissman, Jonathan S

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