TY - JOUR
KW - Cell biology
KW - Data integration
KW - Gastrointestinal Diseases
KW - Immunology
KW - Transcriptomics
AU - Amanda J. Oliver
AU - Ni Huang
AU - Raquel Bartolome-Casado
AU - Ruoyan Li
AU - Simon Koplev
AU - Hogne R. Nilsen
AU - Madelyn Moy
AU - Batuhan Cakir
AU - Krzysztof Polanski
AU - Victoria Gudiño
AU - Elisa Melón-Ardanaz
AU - Dinithi Sumanaweera
AU - Daniel Dimitrov
AU - Lisa Marie Milchsack
AU - Michael E. B. FitzPatrick
AU - Nicholas M. Provine
AU - Jacqueline M. Boccacino
AU - Emma Dann
AU - Alexander V. Predeus
AU - Ken To
AU - Martin Prete
AU - Jonathan A. Chapman
AU - Andrea C. Masi
AU - Emily Stephenson
AU - Justin Engelbert
AU - Sebastian Lobentanzer
AU - Shani Perera
AU - Laura Richardson
AU - Rakeshlal Kapuge
AU - Anna Wilbrey-Clark
AU - Claudia I. Semprich
AU - Sophie Ellams
AU - Catherine Tudor
AU - Philomeena Joseph
AU - Alba Garrido-Trigo
AU - Ana M. Corraliza
AU - Thomas R. W. Oliver
AU - C. Elizabeth Hook
AU - Kylie R. James
AU - Krishnaa T. Mahbubani
AU - Kourosh Saeb-Parsy
AU - Matthias Zilbauer
AU - Julio Saez-Rodriguez
AU - Marte Lie Høivik
AU - Espen S. Bækkevold
AU - Christopher J. Stewart
AU - Janet E. Berrington
AU - Kerstin B. Meyer
AU - Paul Klenerman
AU - Azucena Salas
AU - Muzlifah Haniffa
AU - Frode L. Jahnsen
AU - Rasa Elmentaite
AU - Sarah A. Teichmann
AB - The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease3. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn’s disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner’s glands. Although previously linked to mucosal healing4, we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases.
BT - Nature
DA - 2024-11
DO - 10.1038/s41586-024-07571-1
IS - 8039
LA - en
N2 - The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease3. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn’s disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner’s glands. Although previously linked to mucosal healing4, we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases.
PY - 2024
SP - 699
EP - 707
T2 - Nature
TI - Single-cell integration reveals metaplasia in inflammatory gut diseases
UR - https://www.nature.com/articles/s41586-024-07571-1
VL - 635
Y2 - 2024-11-26
SN - 1476-4687
ER -