Journal Article

Single-cell integration reveals metaplasia in inflammatory gut diseases

Zilbauer, Matthias, Huang, Ni, Nilsen, Hogne R., Chapman, Jonathan A., Moy, Madelyn, James, Kylie R., Teichmann, Sarah A., Stewart, Christopher J., Predeus, Alexander V., Provine, Nicholas M., Garrido-Trigo, Alba, Semprich, Claudia I., Perera, Shani, Mahbubani, Krishnaa T., Kapuge, Rakeshlal, Dimitrov, Daniel, Høivik, Marte Lie, Gudiño, Victoria, Milchsack, Lisa Marie, Engelbert, Justin, Polanski, Krzysztof, Dann, Emma, Elmentaite, Rasa, Oliver, Amanda J., Salas, Azucena, Richardson, Laura, Ellams, Sophie, Koplev, Simon, Prete, Martin, Lobentanzer, Sebastian, Berrington, Janet E., Masi, Andrea C., Meyer, Kerstin B., Wilbrey-Clark, Anna, Sumanaweera, Dinithi, Saez-Rodriguez, Julio, Klenerman, Paul, Oliver, Thomas R. W., Tudor, Catherine, Haniffa, Muzlifah, Li, Ruoyan, Saeb-Parsy, Kourosh, Bartolome-Casado, Raquel, Joseph, Philomeena, Bækkevold, Espen S., To, Ken, Jahnsen, Frode L., FitzPatrick, Michael E. B., Boccacino, Jacqueline M., Hook, C. Elizabeth, Melón-Ardanaz, Elisa, Corraliza, Ana M., Cakir, Batuhan, Stephenson, Emily

2024

Overview

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases 1 , 2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease 3 . 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 healing 4 , 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. The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 38/39 / 38/91 / 45 / 631/114/2401 / 631/250 / 631/337/2019 / 631/80 / 692/699/1503 / Adult / Adults / Annotations / Autoimmune diseases / Automation / Brunner Glands - metabolism / Cancer / Case-Control Studies / Celiac disease / Celiac Disease - pathology / Cells / Child / Chronic illnesses / Colitis, Ulcerative - pathology / Colon / Crohn Disease - immunology / Crohn Disease - pathology / Crohn's Disease / Datasets / Datasets as Topic / Epithelial cells / Epithelial Cells - pathology / Epithelium / Fibroblasts / Gastric Mucosa - immunology / Gastric Mucosa - pathology / Gastrointestinal diseases / Gastrointestinal Diseases - immunology / Gastrointestinal Diseases - pathology / Gastrointestinal Neoplasms - immunology / Gastrointestinal Neoplasms - pathology / Gastrointestinal system / Gastrointestinal tract / Gastrointestinal Tract - immunology / Gastrointestinal Tract - pathology / Gene expression / Gene sequencing / Genomics / Health / Homeostasis / Humanities and Social Sciences / Humans / Immune system / Inflammation / Inflammation - immunology / Inflammation - pathology / Inflammatory bowel disease / Inflammatory bowel diseases / Intestinal Mucosa - immunology / Intestinal Mucosa - pathology / Leukocytes (neutrophilic) / Life span / Lymphocytes / Lymphocytes T / Metaplasia / Metaplasia - pathology / Mucosa / Mucosal immunity / multidisciplinary / Neutrophils / Neutrophils - immunology / Nutrient uptake / Pediatrics / Pylorus - metabolism / Quality Control / Regions / Science / Science (multidisciplinary) / Single-Cell Analysis - methods / Single-Cell Gene Expression Analysis / Small intestine / Stem cells / Stem Cells - immunology / Stem Cells - metabolism / Stem Cells - pathology / Stomach / T-Lymphocytes - immunology / Transcriptomics / Ulcerative colitis