Single-cell integration reveals metaplasia in inflammatory gut diseases

• 成果类型: Article
• 署名作者: Oliver, Amanda J.; Huang, Ni; Bartolome-Casado, Raquel; Li, Ruoyan; Koplev, Simon; Nilsen, Hogne R.; Moy, Madelyn; Cakir, Batuhan; Polanski, Krzysztof; Gudino, Victoria; Melon-Ardanaz, Elisa; Sumanaweera, Dinithi; Dimitrov, Daniel; Milchsack, Lisa Marie; FitzPatrick, Michael E. B.; Provine, Nicholas M.; Boccacino, Jacqueline M.; Dann, Emma; Predeus, Alexander, V; To, Ken; Prete, Martin; Chapman, Jonathan A.; Masi, Andrea C.; Stephenson, Emily; Engelbert, Justin; Lobentanzer, Sebastian; Perera, Shani; Richardson, Laura; Kapuge, Rakeshlal; Wilbrey-Clark, Anna; Semprich, Claudia, I; Ellams, Sophie; Tudor, Catherine; Joseph, Philomeena; Garrido-Trigo, Alba; Corraliza, Ana M.; Oliver, Thomas R. W.; Hook, C. Elizabeth; James, Kylie R.; Mahbubani, Krishnaa T.; Saeb-Parsy, Kourosh; Zilbauer, Matthias; Saez-Rodriguez, Julio; Hoivik, Marte Lie; Baekkevold, Espen S.; Stewart, Christopher J.; Berrington, Janet E.; Meyer, Kerstin B.; Klenerman, Paul; Salas, Azucena; Haniffa, Muzlifah; Jahnsen, Frode L.; Elmentaite, Rasa; Teichmann, Sarah A.
• 署名单位: Wellcome Trust Sanger Institute; University of Oslo; University of Oslo; National Hospital Norway; University of Texas System; UTMD Anderson Cancer Center; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; CIBER - Centro de Investigacion Biomedica en Red; CIBEREHD; Ruprecht Karls University Heidelberg; University of Oxford; Newcastle University - UK; University of Cambridge; University of Cambridge; Garvan Institute of Medical Research; University of New South Wales Sydney; University of Cambridge; University of Cambridge; University of Cambridge; University of Cambridge; University of Cambridge; University of Oslo; University of Oslo; University of Oxford; University of Oxford; Oxford University Hospitals NHS Foundation Trust; Newcastle University - UK; Newcastle Upon Tyne Hospitals NHS Foundation Trust; Newcastle Upon Tyne Hospitals NHS Foundation Trust; University of Cambridge; University of Cambridge; Canadian Institute for Advanced Research (CIFAR)
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4334
• DOI: 10.1038/s41586-024-07571-1
• 发表日期: 2024-11-21
• 页码: 699-+
• 关键词: intestinal epithelial-cells; gene-expression; ulcerative-colitis; gland metaplasia; bowel-disease; landscape; DYNAMICS; atlas

摘要

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.