Faculty, Staff and Student Publications
Publication Date
11-1-2024
Journal
Nature
Abstract
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.
Keywords
Adult, Humans, Brunner Glands, Case-Control Studies, Celiac Disease, Colitis, Ulcerative, Crohn Disease, Datasets as Topic, Epithelial Cells, Gastric Mucosa, Gastrointestinal Diseases, Gastrointestinal Neoplasms, Gastrointestinal Tract, Health, Inflammation, Intestinal Mucosa, Metaplasia, Neutrophils, Pylorus, Quality Control, Single-Cell Analysis, Single-Cell Gene Expression Analysis, Stem Cells, T-Lymphocytes, Child, Cell biology, Immunology, Gastrointestinal diseases, Transcriptomics, Data integration
DOI
10.1038/s41586-024-07571-1
PMID
39567783
PMCID
PMC11578898
PubMedCentral® Posted Date
11-6-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons