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Cells of the human intestinal tract mapped across space and time

Lookup NU author(s): Issac Goh Kai'En, Dr Steven LisgoORCiD, Emily StephensonORCiD, Justin Engelbert, Dr Rachel Botting, Professor Muzlifah Haniffa

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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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