Cells of the human intestinal tract mapped across space and time

Rasa Elmentaite, Natsuhiko Kumasaka, Kenny Roberts, Aaron Fleming, Emma Dann, Hamish W. King, Vitalii Kleshchevnikov, Monika Dabrowska, Sophie Pritchard, Liam Bolt, Sara F. Vieira, Lira Mamanova, Ni Huang, Francesca Perrone, Issac Goh Kai’En, Steven N. Lisgo, Matilda Katan, Steven Leonard, Thomas R. W. Oliver, C. Elizabeth Hook, Komal Nayak, Lia S. Campos, Cecilia Domínguez Conde, Emily Stephenson, Justin Engelbert, Rachel A. Botting, Krzysztof Polanski, Stijn van Dongen, Minal Patel, Michael D. Morgan, John C. Marioni, Omer Ali Bayraktar, Kerstin B. Meyer, Xiaoling He, Roger A. Barker, Holm H. Uhlig, Krishnaa T. Mahbubani, Kourosh Saeb-Parsy, Matthias Zilbauer, Menna R. Clatworthy, Muzlifah Haniffa, Kylie R. James () and Sarah A. Teichmann ()
Additional contact information
Rasa Elmentaite: Wellcome Sanger Institute, Wellcome Genome Campus
Natsuhiko Kumasaka: Wellcome Sanger Institute, Wellcome Genome Campus
Kenny Roberts: Wellcome Sanger Institute, Wellcome Genome Campus
Aaron Fleming: MRC Laboratory of Molecular Biology
Emma Dann: Wellcome Sanger Institute, Wellcome Genome Campus
Hamish W. King: Queen Mary University of London
Vitalii Kleshchevnikov: Wellcome Sanger Institute, Wellcome Genome Campus
Monika Dabrowska: Wellcome Sanger Institute, Wellcome Genome Campus
Sophie Pritchard: Wellcome Sanger Institute, Wellcome Genome Campus
Liam Bolt: Wellcome Sanger Institute, Wellcome Genome Campus
Sara F. Vieira: Wellcome Sanger Institute, Wellcome Genome Campus
Lira Mamanova: Wellcome Sanger Institute, Wellcome Genome Campus
Ni Huang: Wellcome Sanger Institute, Wellcome Genome Campus
Francesca Perrone: University of Cambridge
Issac Goh Kai’En: Newcastle University
Steven N. Lisgo: Newcastle University
Matilda Katan: University College London
Steven Leonard: Wellcome Sanger Institute, Wellcome Genome Campus
Thomas R. W. Oliver: Wellcome Sanger Institute, Wellcome Genome Campus
C. Elizabeth Hook: Cambridge University Hospitals NHS Foundation Trust
Komal Nayak: University of Cambridge
Lia S. Campos: Wellcome Sanger Institute, Wellcome Genome Campus
Cecilia Domínguez Conde: Wellcome Sanger Institute, Wellcome Genome Campus
Emily Stephenson: Newcastle University
Justin Engelbert: Newcastle University
Rachel A. Botting: Newcastle University
Krzysztof Polanski: Wellcome Sanger Institute, Wellcome Genome Campus
Stijn van Dongen: Wellcome Sanger Institute, Wellcome Genome Campus
Minal Patel: Wellcome Sanger Institute, Wellcome Genome Campus
Michael D. Morgan: Wellcome Genome Campus
John C. Marioni: Wellcome Sanger Institute, Wellcome Genome Campus
Omer Ali Bayraktar: Wellcome Sanger Institute, Wellcome Genome Campus
Kerstin B. Meyer: Wellcome Sanger Institute, Wellcome Genome Campus
Xiaoling He: University of Cambridge
Roger A. Barker: University of Cambridge
Holm H. Uhlig: University of Oxford
Krishnaa T. Mahbubani: University of Cambridge and NIHR Cambridge Biomedical Research Centre
Kourosh Saeb-Parsy: University of Cambridge and NIHR Cambridge Biomedical Research Centre
Matthias Zilbauer: University of Cambridge
Menna R. Clatworthy: Wellcome Sanger Institute, Wellcome Genome Campus
Muzlifah Haniffa: Wellcome Sanger Institute, Wellcome Genome Campus
Kylie R. James: Wellcome Sanger Institute, Wellcome Genome Campus
Sarah A. Teichmann: Wellcome Sanger Institute, Wellcome Genome Campus

Nature, 2021, vol. 597, issue 7875, 250-255

Abstract: Abstract 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.

Date: 2021
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Citations: View citations in EconPapers (15)

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DOI: 10.1038/s41586-021-03852-1

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