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Lookup NU author(s): Dr Jon Chapman, Dr Emily StephensonORCiD, Justin Engelbert, Professor Christopher StewartORCiD, Professor Muzlifah Haniffa
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.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.
Author(s): Oliver AJ, Huang N, Bartolome-Casado R, Li R, Koplev S, Nilsen HR, Moy M, Cakir B, Polanski K, Gudino V, Melon-Ardanaz E, Sumanaweera D, Dimitrov D, Milchsack LM, FitzPatrick MEB, Provine NM, Boccacino JM, Dann E, Predeus AV, To K, Prete M, Chapman JA, Masi AC, Stephenson E, Engelbert J, Lobentanzer S, Perera S, Richardson L, Kapuge R, Wilbrey-Clark A, Semprich CI, Ellams S, Tudor C, Joseph P, Garrido-Trigo A, Corraliza AM, Oliver TRW, Hook CE, James KR, Mahbubani KT, Saeb-Parsy K, Zilbauer M, Saez-Rodriguez J, Hoivik ML, Baekkevold ES, Stewart CJ, Berrington JE, Meyer KB, Klenerman P, Salas A, Haniffa M, Jahnsen FL, Elmentaite R, Teichmann SA
Publication type: Article
Publication status: Published
Journal: Nature
Year: 2024
Volume: 635
Issue: 8039
Pages: 699-707
Online publication date: 20/11/2024
Acceptance date: 15/05/2024
Date deposited: 03/12/2024
ISSN (print): 0028-0836
ISSN (electronic): 1476-4687
Publisher: Nature Research
URL: https://doi.org/10.1038/s41586-024-07571-1
DOI: 10.1038/s41586-024-07571-1
Data Access Statement: Raw sequencing data for adult samples are available through Array Express with the accession number E-MTAB-14050. Published data sets are readily available to access through the GEO, ArrayExpress, European Genome-Phenome Archive, BioProject and Broad Institute Single Cell Portal with the accession numbers GSE152042, GSE188478, GSE180544, E-MTAB-11536, E-MTAB-9543, E-MTAB-9536, E-MTAB-8901, GSE159929, E-MTAB-9489, GSE121380, GSE157477, E-MTAB-8007, E-MTAB-8474, E-MTAB-8484, E-MTAB-8486, GSE167297, GSE150290, GSE114374, EGAS00001003779, E-MTAB-8410, GSE122846, PRJEB31843, GSE134809, GSE161267, GSE116222, GSE182270, GSE125970, GSE164241, E-MTAB-10187, E-MTAB-10268 and SCP1884, which are also detailed in Supplementary Table 1. Published bulk RNA-seq datasets are available through the GEO, ArrayExpress and Expression Atlas with the acces sion numbers GSE111889, E-MTAB-5464, E-GEOD-101794, GSE131705, GSE145358 and GSE126299. For the rest of the data access statement please see the paper
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