Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis
| العنوان: | Niche-Specific Reprogramming of Epigenetic Landscapes Drives Myeloid Cell Diversity in Nonalcoholic Steatohepatitis |
|---|---|
| المؤلفون: | Rick Z. Li, Ronald M. Evans, David Gosselin, Ty D. Troutman, Nathanael J. Spann, Martina P. Pasillas, Mojgan Hosseini, Bonne M. Thompson, Hunter Bennett, Verena M. Link, Zhengyu Ouyang, Jeffrey G. McDonald, Ronald N. Germain, Bao Chau T. Vu, Kaori M. Ego, Anita Gola, Mashito Sakai, Xiaoli Sun, Cassi M. Bruni, Ling Wa Chong, Jason S. Seidman, Christopher K. Glass, Joseph L. Witztum |
| المصدر: | Immunity, vol 52, iss 6 Immunity |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell, Epigenesis, Genetic, Hepatitis, Transcriptome, Mice, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, TREM2, 2.1 Biological and endogenous factors, Immunology and Allergy, Macrophage, Myeloid Cells, ATF3, nonalcoholic steatohepatitis, Aetiology, tissue macrophage, Liver Disease, Kupffer cell, High-Throughput Nucleotide Sequencing, Cellular Reprogramming, Phenotype, Cell biology, ChIP-seq, Infectious Diseases, medicine.anatomical_structure, Liver, Cellular Microenvironment, Organ Specificity, 030220 oncology & carcinogenesis, Chromatin Immunoprecipitation Sequencing, LXR, Single-Cell Analysis, Reprogramming, Signal Transduction, Protein Binding, Kupffer Cells, Immunology, Biology, digestive system, Article, 03 medical and health sciences, Genetic, scRNA-seq, genomics, Genetics, medicine, Humans, Animals, Epigenetics, Myeloid Progenitor Cells, epigenetics, Animal, Macrophages, Gene Expression Profiling, medicine.disease, Diet, Disease Models, Animal, Gene Ontology, Good Health and Well Being, 030104 developmental biology, Gene Expression Regulation, Disease Models, Steatohepatitis, Digestive Diseases, Biomarkers, Epigenesis |
| الوصف: | Tissue-resident and recruited macrophages contribute to both host defense and pathology. Multiple macrophage phenotypes are represented in diseased tissues, but we lack deep understanding of mechanisms controlling diversification. Here, we investigate origins and epigenetic trajectories of hepatic macrophages during diet-induced non-alcoholic steatohepatitis (NASH). The NASH diet induced significant changes in Kupffer cell enhancers and gene expression, resulting in partial loss of Kupffer cell identity, induction of Trem2 and Cd9 expression, and cell death. Kupffer cell loss was compensated by gain of adjacent monocyte-derived macrophages that exhibited convergent epigenomes, transcriptomes, and functions. NASH-induced changes in Kupffer cell enhancers were driven by AP-1 and EGR that reprogrammed LXR functions required for Kupffer cell identity and survival to instead drive a scar-associated macrophage phenotype. These findings reveal mechanisms by which disease-associated environmental signals instruct resident and recruited macrophages to acquire distinct gene expression programs and corresponding functions. |
| وصف الملف: | application/pdf |
| تدمد: | 1074-7613 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b26572f341494c60eb8695f7b7d03ef https://doi.org/10.1016/j.immuni.2020.04.001 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0b26572f341494c60eb8695f7b7d03ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10747613 |
|---|