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Lookup NU author(s): Issac Goh Kai'EnORCiD, Dr Steven LisgoORCiD, Dr Emily StephensonORCiD, Justin Engelbert, Dr Rachel Botting, Professor Muzlifah Haniffa
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021, The Author(s).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.
Author(s): Elmentaite R, Kumasaka N, Roberts K, Fleming A, Dann E, King HW, Kleshchevnikov V, Dabrowska M, Pritchard S, Bolt L, Vieira SF, Mamanova L, Huang N, Perrone F, Goh Kai'En I, Lisgo SN, Katan M, Leonard S, Oliver TRW, Hook CE, Nayak K, Campos LS, Dominguez Conde C, Stephenson E, Engelbert J, Botting RA, Polanski K, van Dongen S, Patel M, Morgan MD, Marioni JC, Bayraktar OA, Meyer KB, He X, Barker RA, Uhlig HH, Mahbubani KT, Saeb-Parsy K, Zilbauer M, Clatworthy MR, Haniffa M, James KR, Teichmann SA
Publication type: Article
Publication status: Published
Journal: Nature
Year: 2021
Volume: 597
Issue: 7875
Pages: 250-255
Print publication date: 09/08/2021
Online publication date: 08/09/2021
Acceptance date: 26/07/2021
Date deposited: 23/09/2021
ISSN (print): 0028-0836
ISSN (electronic): 1476-4687
Publisher: Nature Research
URL: https://doi.org/10.1038/s41586-021-03852-1
DOI: 10.1038/s41586-021-03852-1
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