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Nature. 2019 Apr 8. doi: 10.1038/s41586-019-1127-1. [Epub ahead of print]

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

Author information

1
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
2
Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3
Flow Cytometry Core Facility, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
4
10x Genomics, Pleasanton, CA, USA.
5
Terry Fox Laboratory, BC Cancer, Vancouver, British Columbia, Canada.
6
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA. hadj@mskcc.org.
7
Computational & Systems Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA. peerd@mskcc.org.

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.

PMID:
30959515
DOI:
10.1038/s41586-019-1127-1

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