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Cells of the human intestinal tract mapped across space and time

Author

Listed:
  • 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
    Cambridge University Hospitals NHS Foundation Trust)

  • 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
    University of Cambridge)

  • John C. Marioni

    (Wellcome Sanger Institute, Wellcome Genome Campus
    Wellcome Genome Campus
    University of Cambridge)

  • 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
    University of Oxford
    NIHR Oxford Biomedical Research Centre)

  • 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
    Cambridge University Hospitals Trust
    University of Cambridge)

  • Menna R. Clatworthy

    (Wellcome Sanger Institute, Wellcome Genome Campus
    MRC Laboratory of Molecular Biology)

  • Muzlifah Haniffa

    (Wellcome Sanger Institute, Wellcome Genome Campus
    Newcastle University
    Newcastle Hospitals NHS Foundation Trust)

  • Kylie R. James

    (Wellcome Sanger Institute, Wellcome Genome Campus
    The Kinghorn Cancer Centre)

  • Sarah A. Teichmann

    (Wellcome Sanger Institute, Wellcome Genome Campus
    University of Cambridge)

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.

Suggested Citation

  • 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 Mam, 2021. "Cells of the human intestinal tract mapped across space and time," Nature, Nature, vol. 597(7875), pages 250-255, September.
  • Handle: RePEc:nat:nature:v:597:y:2021:i:7875:d:10.1038_s41586-021-03852-1
    DOI: 10.1038/s41586-021-03852-1
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    Cited by:

    1. Carmen Aguilar & Mindaugas Pauzuolis & Malvika Pompaiah & Ehsan Vafadarnejad & Panagiota Arampatzi & Mara Fischer & Dominik Narres & Mastura Neyazi & Özge Kayisoglu & Thomas Sell & Nils Blüthgen & Mar, 2022. "Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Egle Kvedaraite & Magda Lourda & Natalia Mouratidou & Tim Düking & Avinash Padhi & Kirsten Moll & Paulo Czarnewski & Indranil Sinha & Ioanna Xagoraris & Efthymia Kokkinou & Anastasios Damdimopoulos & , 2024. "Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Yue Wang & Yanbo Yu & Lixiang Li & Mengqi Zheng & Jiawei Zhou & Haifan Gong & Bingcheng Feng & Xiao Wang & Xuanlin Meng & Yanyan Cui & Yanan Xia & Shuzheng Chu & Lin Lin & Huijun Chang & Ruchen Zhou &, 2023. "Bile acid-dependent transcription factors and chromatin accessibility determine regional heterogeneity of intestinal antimicrobial peptides," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Nannan Guo & Na Li & Li Jia & Qinyue Jiang & Mette Schreurs & Vincent Unen & Susana M. Chuva Sousa Lopes & Alexandra A. Vloemans & Jeroen Eggermont & Boudewijn Lelieveldt & Frank J. T. Staal & Noel F., 2023. "Immune subset-committed proliferating cells populate the human foetal intestine throughout the second trimester of gestation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Reza Mirzazadeh & Zaneta Andrusivova & Ludvig Larsson & Phillip T. Newton & Leire Alonso Galicia & Xesús M. Abalo & Mahtab Avijgan & Linda Kvastad & Alexandre Denadai-Souza & Nathalie Stakenborg & Ale, 2023. "Spatially resolved transcriptomic profiling of degraded and challenging fresh frozen samples," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Jia Li & Alan J. Simmons & Caroline V. Hawkins & Sophie Chiron & Marisol A. Ramirez-Solano & Naila Tasneem & Harsimran Kaur & Yanwen Xu & Frank Revetta & Paige N. Vega & Shunxing Bao & Can Cui & Regin, 2024. "Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn’s disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    7. Pietro Demela & Nicola Pirastu & Blagoje Soskic, 2023. "Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Ohman Kwon & Hana Lee & Jaeeun Jung & Ye Seul Son & Sojeong Jeon & Won Dong Yoo & Naeun Son & Kwang Bo Jung & Eunho Choi & In-Chul Lee & Hyung-Jun Kwon & Chuna Kim & Mi-Ok Lee & Hyun-Soo Cho & Dae Soo, 2024. "Chemically-defined and scalable culture system for intestinal stem cells derived from human intestinal organoids," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Jiarui Ding & John J. Garber & Amiko Uchida & Ariel Lefkovith & Grace T. Carter & Praveen Vimalathas & Lauren Canha & Michael Dougan & Kyle Staller & Joseph Yarze & Toni M. Delorey & Orit Rozenblatt-R, 2024. "An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    10. Alberto Díez-Sánchez & Håvard T. Lindholm & Pia M. Vornewald & Jenny Ostrop & Rouan Yao & Andrew B. Single & Anne Marstad & Naveen Parmar & Tovah N. Shaw & Mara Martín-Alonso & Menno J. Oudhoff, 2024. "LSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    11. Susanne Kessler & Bradly Burke & Geoffroy Andrieux & Jan Schinköthe & Lea Hamberger & Johannes Kacza & Shijun Zhan & Clara Reasoner & Taru S. Dutt & Maria Kaukab Osman & Marcela Henao-Tamayo & Julian , 2024. "Deciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Akshaya Ramakrishnan & Aikaterini Symeonidi & Patrick Hanel & Katharina T. Schmid & Maria L. Richter & Michael Schubert & Maria Colomé-Tatché, 2023. "epiAneufinder identifies copy number alterations from single-cell ATAC-seq data," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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