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Journal Article

Molecular recording of mammalian Embryogenesis

MPS-Authors
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Grosswendt,  Stefanie
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Kretzmer,  Helene
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Meissner,  Alexander
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Chan2019.pdf
(Publisher version), 10MB

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Citation

Chan, M. M., Smith, Z. D., Grosswendt, S., Kretzmer, H., Norman, T. M., Adamson, B., et al. (2019). Molecular recording of mammalian Embryogenesis. Nature, 570(7759), 77-82. doi:10.1038/s41586-019-1184-5.


Cite as: http://hdl.handle.net/21.11116/0000-0004-9923-8
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.