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Charting the emergent organotypic landscape of the mammalian gut endoderm at single-cell resolution

By Sonja Nowotschin, Manu Setty, Ying-Yi Kuo, Vincent Lui, Vidur Garg, Roshan Sharma, Claire S Simon, Nestor Saiz, Rui Gardner, Stéphane C Boutet, Deanna M Church, Pamela A Hoodless, Anna-Katerina Hadjantonakis, Dana Pe’er

Posted 15 Nov 2018
bioRxiv DOI: 10.1101/471078

To comprehensively delineate the ontogeny of an organ system, we generated 112,217 single-cell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatio-temporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis.

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