Epigenetic and Transcriptional Programming of Esophageal Eosinophils by the Local Tissue Environment [ATAC-seq]
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ABSTRACT:
PROVIDER: PRJNA1090517 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic and Transcriptional Programming of Esophageal Eosinophils by the Local Tissue Environment
| PRJNA1090515 | ENA
Project description:Tissue eosinophilia is a hallmark feature of allergic diseases. Eosinophils resident in different tissues have unique properties, and whether that heterogeneity is stochastic or regulated by cell-intrinsic or extrinsic factors has not been established. We profiled tissue eosinophils in the esophagus during allergic inflammation using single-cell sequencing, epigenomic mapping, and flow cytometry. Human and murine esophageal eosinophils exhibited a specialized transcriptional and epigenetic landscape, composed of metabolic, extracellular sensing, and immunomodulatory genes, and enriched for AP-1 transcription factor binding sites. Additionally, human esophageal eosinophils were enriched for genes present within allergic disease risk loci and genes that correlated with the degree of esophageal eosinophilia. Furthermore, the esophageal eosinophil molecular signature was regulated by interactions between eosinophils and esophageal epithelial cells. Taken together, we determined that esophageal eosinophils are programmed through interactions with epithelial cells by interplay of local tissue extrinsic factors that operate through a transcription factor complex containing AP-1.
2025-09-04 | GSE262177 | GEO
Project description:Tissue eosinophilia is a hallmark feature of allergic diseases. Eosinophils resident in different tissues have unique properties, and whether that heterogeneity is stochastic or regulated by cell-intrinsic or extrinsic factors has not been established. We profiled tissue eosinophils in the esophagus during allergic inflammation using single-cell sequencing, epigenomic mapping, and flow cytometry. Human and murine esophageal eosinophils exhibited a specialized transcriptional and epigenetic landscape, composed of metabolic, extracellular sensing, and immunomodulatory genes, and enriched for AP-1 transcription factor binding sites. Additionally, human esophageal eosinophils were enriched for genes present within allergic disease risk loci and genes that correlated with the degree of esophageal eosinophilia. Furthermore, the esophageal eosinophil molecular signature was regulated by interactions between eosinophils and esophageal epithelial cells. Taken together, we determined that esophageal eosinophils are programmed through interactions with epithelial cells by interplay of local tissue extrinsic factors that operate through a transcription factor complex containing AP-1.
2025-09-04 | GSE262175 | GEO
Project description:Epigenetic and Transcriptional Programming of Esophageal Eosinophils by the Local Tissue Environment [scRNA-seq]
| PRJNA1090521 | ENA
Project description:Eosinophils are present in several solid tumors and have context-dependent function. The role of eosinophils in the development of esophageal squamous cell cancer (ESCC), 85% of esophageal cancers worldwide, is unknown. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks followed by vehicle for 8 weeks to induce esophageal squamous pre-cancer. Eosinophil depletion using three mouse models resulted in exacerbated 4-NQO tumorigenesis. RNA-sequencing on the whole esophagus of WT and ?dblGATA mice was done in the pre-cancer model to understand how the presence of eosinophils affects the pre-cancer esophageal environment.
2023-12-01 | GSE233443 | GEO
Project description:Eosinophils are present in several solid tumors and have context-dependent function. The role of eosinophils in the development of esophageal squamous cell cancer (ESCC), 85% of esophageal cancers worldwide, is unknown. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks followed by vehicle for 8 weeks to induce esophageal squamous pre-cancer. Eosinophil depletion using three mouse models resulted in exacerbated 4-NQO tumorigenesis. In order to study the transcriptional profiles of eosinophils specifically, we isolated eosinophils from esophageal tissue of WT mice which had been treated with 4-NQO in the pre-cancer model. Because eosinophils are not present in the esophagus normally, we isolated eosinophils from the colons of a random subset of the same mice. Additionally, we derived eosinophils from the bone marrow of a random subset of the same mice.
2023-12-01 | GSE233448 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-09-04 | GSE262178 | GEO
Project description:Eosinophils are elusive cells involved in allergic inflammation. Herein, we profiled 586 human eosinophils from the circulation and an allergic inflammatory site, the esophagus, of patients with eosinophilic esophagitis by Seq-Well–based single-cell RNA sequencing. The esophageal eosinophils were composed of a population of activated eosinophils (enriched in 659 genes compared with peripheral blood-associated eosinophils) and a small population of eosinophils resembling peripheral blood eosinophils (enriched in 62 genes compared with esophageal eosinophils). Esophageal eosinophils expressed genes involved in sensing and responding to diverse stimuli, most notably interferon-Ɣ(IFN-Ɣ), interleukin 10 (IL-10), histamine and leukotrienes, and succinate metabolite signaling. Esophageal eosinophils were most distinguished from other esophageal populations by gene expression of the receptors CCR3, HRH4, SUCNR1, and VSTM1; transcription factors CEBPE, OLIG1, and OLIG2; protease PRSS33; and hallmark eosinophil gene CLC. A web of bidirectional eosinophil interactions with other myeloid cells, T cells, fibroblasts, and the epithelium and vasculature was derived. Comparing esophageal eosinophils and mast cells revealed that esophageal eosinophils expressed genes involved in DAP12 interactions, IgG receptor-triggered events, immunoregulation, and IL-10 signaling, whereas esophageal mast cells expressed genes involved in arachidonic acid metabolism and response to unfolded proteins. These findings indicate that esophageal eosinophils exist as two populations, a minority population resembling blood eosinophils and the other population characterized by high de novo transcription of diverse sensing receptors and inflammatory mediators readying them to intersect with diverse cell types.
2024-08-09 | GSE256088 | GEO
Project description:Intestinal homeostasis following postnatal microbial colonization requires the coordination of multiple processes, including the activation of immune cells, cell-cell communication, the controlled deposition of extracellular matrix, and epithelial cell turnover and differentiation. The intestine harbors the largest frequency of resident eosinophils of all homeostatic organs, yet the functional significance of eosinophil residence in the gut remains unclear. Eosinophils are equipped to both respond to, and modify, their local tissue environment and thus are able to regulate the adaption of tissues to environmental changes. We report a critical role for eosinophils in regulating villous structure, barrier integrity and motility in the small intestine. Notably, the microbiota was identified as a key driver of small intestinal eosinophil activation and function. Collectively our findings demonstrate a critical role for eosinophils in facilitating mutualistic interactions between host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.
2025-08-27 | PXD032084 | Pride
Project description:To determine how eosinophils adapt to the intestinal environment, eosinophils were sorted from the bone marrow and small intestine and compared by RNA sequencing. We show here that intestinal eosinophils were specifically adapted to their environment and underwent substantial transcriptomic changes. Intestinal eosinophils upregulated genes relating to the immune response and cell-cell communication, extracellular matrix components and metalloproteases, and the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor with broad functions in intestinal homeostasis.
2022-02-25 | GSE185070 | GEO