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Cells of the human intestinal tract mapped across space and time.

Published version
Peer-reviewed

Type

Article

Change log

Authors

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.

Description

Funder: Medical Research Council

Keywords

Intestines, Enteric Nervous System, Lymph Nodes, Epithelial Cells, Fetus, Animals, Mice, Inbred C57BL, Humans, Mice, Crohn Disease, Receptors, IgG, Signal Transduction, Aging, Organogenesis, Time Factors, Adult, Child, Health, Female, Spatio-Temporal Analysis, Datasets as Topic

Journal Title

Nature

Conference Name

Journal ISSN

0028-0836

Volume Title

597

Publisher

Sponsorship
European Research Council (646794)
Wellcome Trust (WT206194, 203151/Z/16/Z, 213555/Z/18/Z, 220268/Z/20/Z, 206194, MR/R006237/1)