@article{4666, keywords = {Cell biology, Data integration, Gastrointestinal Diseases, Immunology, Transcriptomics}, author = {Amanda J. Oliver and Ni Huang and Raquel Bartolome-Casado and Ruoyan Li and Simon Koplev and Hogne R. Nilsen and Madelyn Moy and Batuhan Cakir and Krzysztof Polanski and Victoria Gudiño and Elisa Melón-Ardanaz and Dinithi Sumanaweera and Daniel Dimitrov and Lisa Marie Milchsack and Michael E. B. FitzPatrick and Nicholas M. Provine and Jacqueline M. Boccacino and Emma Dann and Alexander V. Predeus and Ken To and Martin Prete and Jonathan A. Chapman and Andrea C. Masi and Emily Stephenson and Justin Engelbert and Sebastian Lobentanzer and Shani Perera and Laura Richardson and Rakeshlal Kapuge and Anna Wilbrey-Clark and Claudia I. Semprich and Sophie Ellams and Catherine Tudor and Philomeena Joseph and Alba Garrido-Trigo and Ana M. Corraliza and Thomas R. W. Oliver and C. Elizabeth Hook and Kylie R. James and Krishnaa T. Mahbubani and Kourosh Saeb-Parsy and Matthias Zilbauer and Julio Saez-Rodriguez and Marte Lie Høivik and Espen S. Bækkevold and Christopher J. Stewart and Janet E. Berrington and Kerstin B. Meyer and Paul Klenerman and Azucena Salas and Muzlifah Haniffa and Frode L. Jahnsen and Rasa Elmentaite and Sarah A. Teichmann}, title = {Single-cell integration reveals metaplasia in inflammatory gut diseases}, 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.}, year = {2024}, journal = {Nature}, volume = {635}, pages = {699-707}, month = {2024-11}, issn = {1476-4687}, url = {https://www.nature.com/articles/s41586-024-07571-1}, doi = {10.1038/s41586-024-07571-1}, language = {en}, }