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

Nowotschin, S.; Setty, M.; Kuo, Y.-Y.; Liu, V.; Garg, V.; Sharma, R.; Simon, C. S.; Saiz, N.; Gardner, R.; Boutet, S. C.; Church, D. M.; Hoodless, P. A.; Hadjantonakis, A.-K.; Pe'er, D.

doi:10.1101/471078

bioRxiv · 10.1101/471078

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

Nowotschin, S.·Setty, M.·Kuo, Y.-Y.·Liu, V.·Garg, V.·Sharma, R.·Simon, C. S.·Saiz, N.·Gardner, R.·Boutet, S. C.·Church, D. M.·Hoodless, P. A.·Hadjantonakis, A.-K.·Pe'er, D.

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Abstract

To comprehensively delineate the ontogeny of an organ system, we generated 112,217 singlecell 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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Nowotschin, S., Setty, M., Kuo, Y.-Y., Liu, V., Garg, V., Sharma, R., Simon, C. S., Saiz, N., Gardner, R., Boutet, S. C., Church, D. M., Hoodless, P. A., Hadjantonakis, A.-K., Pe'er, D.. 2018-11-15. Charting the emergent organotypic landscape of the mammalian gut endoderm at single-cell resolution. https://doi.org/10.1101/471078

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