TY - JOUR
KW - Adult
KW - aging
KW - Animals
KW - Child
KW - Crohn Disease
KW - Datasets as Topic
KW - Enteric Nervous System
KW - Epithelial Cells
KW - Female
KW - Fetus
KW - Health
KW - Humans
KW - Intestines
KW - Lymph Nodes
KW - Mice
KW - Mice, Inbred C57BL
KW - Organogenesis
KW - Receptors, IgG
KW - Signal Transduction
KW - Spatio-Temporal Analysis
KW - Time Factors
AU - Rasa Elmentaite
AU - Natsuhiko Kumasaka
AU - Kenny Roberts
AU - Aaron Fleming
AU - Emma Dann
AU - Hamish W. King
AU - Vitalii Kleshchevnikov
AU - Monika Dabrowska
AU - Sophie Pritchard
AU - Liam Bolt
AU - Sara F. Vieira
AU - Lira Mamanova
AU - Ni Huang
AU - Francesca Perrone
AU - Issac Goh Kai'En
AU - Steven N. Lisgo
AU - Matilda Katan
AU - Steven Leonard
AU - Thomas R. W. Oliver
AU - C. Elizabeth Hook
AU - Komal Nayak
AU - Lia S. Campos
AU - Cecilia Domínguez Conde
AU - Emily Stephenson
AU - Justin Engelbert
AU - Rachel A. Botting
AU - Krzysztof Polanski
AU - Stijn van Dongen
AU - Minal Patel
AU - Michael D. Morgan
AU - John C. Marioni
AU - Omer Ali Bayraktar
AU - Kerstin B. Meyer
AU - Xiaoling He
AU - Roger A. Barker
AU - Holm H. Uhlig
AU - Krishnaa T. Mahbubani
AU - Kourosh Saeb-Parsy
AU - Matthias Zilbauer
AU - Menna R. Clatworthy
AU - Muzlifah Haniffa
AU - Kylie R. James
AU - Sarah A. Teichmann
AB - 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.
BT - Nature
DA - 2021-09
DO - 10.1038/s41586-021-03852-1
IS - 7875
LA - eng
N2 - 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.
PY - 2021
SP - 250
EP - 255
T2 - Nature
TI - Cells of the human intestinal tract mapped across space and time
VL - 597
SN - 1476-4687
ER -