Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease

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• dc.contributor.author Garrido Trigo, Alba
• dc.contributor.author Marchese, Domenica, 1986-
• dc.contributor.author Caratù, Ginevra
• dc.contributor.author Heyn, Holger
• dc.contributor.author Salas, Azucena
• dc.date.accessioned 2023-11-06T07:41:57Z
• dc.date.available 2023-11-06T07:41:57Z
• dc.date.issued 2023
• dc.description.abstract Ulcerative colitis and Crohn's disease are chronic inflammatory intestinal diseases with perplexing heterogeneity in disease manifestation and response to treatment. While the molecular basis for this heterogeneity remains uncharacterized, single-cell technologies allow us to explore the transcriptional states within tissues at an unprecedented resolution which could further understanding of these complex diseases. Here, we apply single-cell RNA-sequencing to human inflamed intestine and show that the largest differences among patients are present within the myeloid compartment including macrophages and neutrophils. Using spatial transcriptomics in human tissue at single-cell resolution (CosMx Spatial Molecular Imaging) we spatially localize each of the macrophage and neutrophil subsets identified by single-cell RNA-sequencing and unravel further macrophage diversity based on their tissue localization. Finally, single-cell RNA-sequencing combined with single-cell spatial analysis reveals a strong communication network involving macrophages and inflammatory fibroblasts. Our data sheds light on the cellular complexity of these diseases and points towards the myeloid and stromal compartments as important cellular subsets for understanding patient-to-patient heterogeneity.
• dc.description.sponsorship This work was funded by grant PID2021-123918OB-I00 from MCIN/AEI/ 10.13039/501100011033 and co-funded by “FEDER A way to make Europe”. AM-C, VG and ID were funded by grant Grant #2008-04050 from The Leona and Harry B. Helmsley Charitable Trust. EM-A is funded by grant RH042155 (RTI2018-096946-B-I00) from Ministerio de Ciencia e Innovacion. IA-T is funded by grant 831434-2 (CE_IMI2-2018-14 call). HH received support for the project PID2020-115439GB-I00- funded by MCIN/AEI/10.13039/501100011033. This publication is part of a project that has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 831434. This project also has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 848028.
• dc.format.mimetype application/pdf
• dc.identifier.citation Garrido-Trigo A, Corraliza AM, Veny M, Dotti I, Melón-Ardanaz E, Rill A, et al. Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease. Nat Commun. 2023 Jul 26;14(1):4506. DOI: 10.1038/s41467-023-40156-6
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-023-40156-6
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/58212
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Commun. 2023 Jul 26;14(1):4506
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/831434
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-123918OB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-096946-B-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-115439GB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848028
• dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Imaging the immune system
• dc.subject.keyword Inflammatory bowel disease
• dc.subject.keyword Mucosal immunology
• dc.subject.keyword Single-cell imaging
• dc.title Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion