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Cells of the human intestinal tract mapped across space and time


The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.

Type Journal
ISBN 1476-4687 (Electronic) 0028-0836 (Linking)
Authors Elmentaite, R.; Kumasaka, N.; Roberts, K.; Fleming, A.; Dann, E.; King, H. W.; Kleshchevnikov, V.; Dabrowska, M.; Pritchard, S.; Bolt, L.; Vieira, S. F.; Mamanova, L.; Huang, N.; Perrone, F.; Goh Kai'En, I.; Lisgo, S. N.; Katan, M.; Leonard, S.; Oliver, T. R. W.; Hook, C. E.; Nayak, K.; Campos, L. S.; Dominguez Conde, C.; Stephenson, E.; Engelbert, J.; Botting, R. A.; Polanski, K.; van Dongen, S.; Patel, M.; Morgan, M. D.; Marioni, J. C.; Bayraktar, O. A.; Meyer, K. B.; He, X.; Barker, R. A.; Uhlig, H. H.; Mahbubani, K. T.; Saeb-Parsy, K.; Zilbauer, M.; Clatworthy, M. R.; Haniffa, M.; James, K. R.; Teichmann, S. A.
Publisher Name NATURE
Published Date 2021-09-30
Published Volume 597
Published Issue 7875
Published Pages 250-255
Status Published in-print
DOI 10.1038/s41586-021-03852-1
URL link to publisher's version