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Nature. 2019 Jun;570(7759):77-82. doi: 10.1038/s41586-019-1184-5. Epub 2019 May 13.

Molecular recording of mammalian embryogenesis.

Chan MM1,2, Smith ZD3,4,5, Grosswendt S6, Kretzmer H6, Norman TM1,2, Adamson B1,2,7, Jost M1,2,8, Quinn JJ1,2, Yang D1,2, Jones MG1,2,9, Khodaverdian A10,11, Yosef N10,11,12,13, Meissner A14,15,16, Weissman JS17,18.

Author information

1
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
2
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
3
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
4
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
5
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
6
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
7
Department of Molecular Biology, Lewis Sigler Institute, Princeton University, Princeton, NJ, USA.
8
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
9
Integrative Program in Quantitative Biology, University of California, San Francisco, San Francisco, CA, USA.
10
Department of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA, USA.
11
Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
12
Chan Zuckerberg Biohub, San Francisco, CA, USA.
13
Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, Cambridge, MA, USA.
14
Broad Institute of MIT and Harvard, Cambridge, MA, USA. meissner@molgen.mpg.de.
15
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA. meissner@molgen.mpg.de.
16
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany. meissner@molgen.mpg.de.
17
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA. jonathan.weissman@ucsf.edu.
18
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA. jonathan.weissman@ucsf.edu.

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.

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PMID:
31086336
DOI:
10.1038/s41586-019-1184-5
[Indexed for MEDLINE]

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