Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease.
Alba Garrido-Trigo, Ana M Corraliza, Marisol Veny, Isabella Dotti, Elisa Melón-Ardanaz, Aina Rill, Helena L Crowell, Ángel Corbí, Victoria Gudiño, Miriam Esteller, Iris Álvarez-Teubel, Daniel Aguilar, M Carme Masamunt, Emily Killingbeck, Youngmi Kim, Michael Leon, Sudha Visvanathan, Domenica Marchese, Ginevra Caratù, Albert Martin-Cardona, Maria Esteve, Julian Panés, Elena Ricart, Elisabetta Mereu, Holger Heyn, Azucena Salas
Published in July 2023, Nature communications.
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.