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The emergent landscape of the mouse gut endoderm at single-cell resolution

Nature (2019) | Download Citation

Abstract

To delineate the ontogeny of the mammalian endoderm, we generated 112,217 single-cell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. By using graph-based approaches, we modelled differentiating cells for spatio-temporal characterization of developmental trajectories and defined the transcriptional architecture that accompanies the emergence of the first (primitive or extra-embryonic) endodermal population and its sister pluripotent (embryonic) epiblast lineage. We uncovered a relationship between descendants of these two lineages, whereby epiblast cells differentiate into endoderm at two distinct time points, before and during gastrulation. Trajectories of endoderm cells were mapped as they acquired embryonic versus extra-embryonic fates, and as they spatially converged within the nascent gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observed the regionalized identity of cells along the anterior–posterior axis of the emergent gut tube, reflecting their embryonic or extra-embryonic origin, and their coordinate patterning into organ-specific territories.

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Author information

Author notes

  1. These authors contributed equally: Sonja Nowotschin, Manu Setty.

Affiliations

  1. Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    • Sonja Nowotschin
    • , Ying-Yi Kuo
    • , Vidur Garg
    • , Claire S. Simon
    • , Nestor Saiz
    •  & Anna-Katerina Hadjantonakis
  2. Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    • Manu Setty
    • , Vincent Liu
    • , Roshan Sharma
    •  & Dana Pe’er
  3. Flow Cytometry Core Facility, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    • Rui Gardner
  4. 10x Genomics, Pleasanton, CA, USA

    • Stéphane C. Boutet
    •  & Deanna M. Church
  5. Terry Fox Laboratory, BC Cancer, Vancouver, British Columbia, Canada

    • Pamela A. Hoodless

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Corresponding authors

Correspondence to Anna-Katerina Hadjantonakis or Dana Pe’er.

Supplementary information

  1. Supplementary Information

    This file contains Supplementary Notes, Supplementary Figures 6-11, and Supplementary References.

  2. Reporting Summary

  3. Supplementary Figures 1-5

  4. Supplementary Table 1

    List of differentially expressed genes for E3.5 clusters.

  5. Supplementary Table 2

    List of differentially expressed genes for E4.5 clusters.

  6. Supplementary Table 3

    List of clusters of genes with similar dynamics in EPI and VE differentiation from E3.5-E5.5.

  7. Supplementary Table 4

    List of genes that are exVE and emVE specific at E5.5.

  8. Supplementary Table 5

    List of genes that are most predictive of VE and DE classes in the E7.5 classifier.

  9. Supplementary Table 6

    List of differentially expressed genes in the E8.75 gut tube clusters.

  10. Supplementary Table 7

    mRNA in situ hybridization probes:

  11. Supplementary Table 8

    mRNA in situ hybridization probes cloned from E8.5 embryo RNA by RT-PCR.

  12. Supplementary Table 9

    Antibodies.

  13. Supplementary Table 10

    Chemicals.

  14. Supplementary Table 11

    Materials.

  15. Supplementary Table 12

    Numbers of GFP+ and GFP- cells in gut tubes of 13ss embryos.

  16. Supplementary Table 13

    List of bulk RNA-seq samples.

  17. Supplementary Table 14

    Palantir parameters.

About this article

Publication history

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DOI

https://doi.org/10.1038/s41586-019-1127-1

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