Year: 2025
Type: article
Abstract: Eosinophils accumulate in different tissues in allergies, cancer, and infectious diseases, adopting distinct properties. Herein, we profiled murine esophageal eosinophils during allergic inflammation using single-cell sequencing, epigenomic mapping, and flow cytometry. Esophageal eosinophils displayed an altered chromatin accessibility profile compared to bone marrow eosinophils, with 761 epi-transcriptionally regulated genes enriched in inflammation, immunoregulation, bacterial sensing, angiogenesis, migration, and apoptosis. The local environment entrains the unique esophageal eosinophil immunophenotype, as suggested by eosinophil-esophageal epithelial co-cultures, esophageal eosinophil transcriptional similarities regardless of the upstream cytokines driving their esophageal localization, and transcription factor gene editing altering esophageal eosinophilia and the associated eosinophil and global esophageal transcriptomes. Finally, the epigenomic and transcriptomic properties of murine esophageal eosinophils are largely conserved in humans. Thus, our data indicate that tissue specialization of esophageal eosinophils is entrained by local environmental cues that induce genome-wide epigenetic reprogramming and regulated by discrete transcription factors and provide a public, epigenetic database of murine tissue eosinophils. Eosinophils exist as a functionally heterogeneous population. Whether the heterogeneity is driven by cell-intrinsic or extrinsic factors is underexplored. Here, by leveraging single-cell transcriptomic data and epigenomic analysis, the authors propose that local environmental cues define the gene expression program of murine esophageal eosinophils and identify AP-1 family members, including ATF3, as key regulators of gene expression.
Source: Nature Communications
Authors: Jennifer M. Felton, Lee E. Edsall, Ty D. Troutman, Lydia Mack, Michael Kotliar, Netali Ben-Baruch Morgenstern, Annalise M. Psaila, Mark Rochman, Andrea M. Klingler, Garrett A. Osswald, Simin Zhang, Julia L. M. Dunn, Ben Wronowski, Tetsuo Shoda, Julie M. Caldwell, Rana Herro, Artem Barski, Kate G. R. Quinlan, Matthew T. Weirauch, Marc E. Rothenberg
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, American Association for the Study of Liver Diseases, Cincinnati Children's Hospital Medical Center, Buckeye Career Center Foundation, Campaign Urging Research for Eosinophilic Disease, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G166906552, G1744546602, G2225868891, G2993597392, G3834737536, Metabotropic Glutamate Receptor Signaling and Extinction Learning, G4881574631, G5508203092, Discovery of eosinophil-derived thermogenic beiging factors to combat obesity, ZE5 Analytical Cytometer, G7956675390, IMMUNOGENETICS OF TRICHINELLA SPIRALIS INTHE MOUSE, G809226465, G9000087880, G9000109998, G9000295917, Cincinnati Rheumatic Diseases Resource Center
OpenAlex ID: W4416631726