Schwartz, Uwe and Prada, Maria Llamazares and Pohl, Stephanie T. and Richter, Mandy and Tamas, Raluca and Schuler, Michael and Keller, Corinna and Mijosek, Vedrana and Muley, Thomas and Schneider, Marc A. and Quast, Karsten and Hey, Joschka and Heussel, Claus P. and Warth, Arne and Winter, Hauke and Sercin, Oezdemirhan and Karmouty-Quintana, Harry and Jyothula, Soma S. K. and Patel, Manish K. and Herth, Felix and Koch, Ina and Petrosino, Giuseppe and Titimeaua, Alexandru and Mardin, Balca R. and Weichenhan, Dieter and Jurkowski, Tomasz P. and Imbusch, Charles D. and Brors, Benedikt and Benes, Vladimir and Jung, Birgit and Wyatt, David and Stahl, Heiko F. and Plass, Christoph and Jurkowska, Renata Z. (2023) High-resolution transcriptomic and epigenetic profiling identifies novel regulators of COPD. EMBO JOURNAL, 42 (12). ISSN 0261-4189, 1460-2075
Full text not available from this repository. (Request a copy)Abstract
Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages. We show that the epigenetic landscape is changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked to fibroblast repair processes using phenotypic screens. Our study provides high-resolution multi-omic maps of HLFs across COPD stages. We reveal novel transcriptomic and epigenetic signatures associated with COPD onset and progression and identify new candidate regulators involved in the pathogenesis of chronic lung diseases. The presence of various epigenetic factors among the candidates demonstrates that epigenetic regulation in COPD is an exciting research field that holds promise for novel therapeutic avenues for patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OBSTRUCTIVE PULMONARY-DISEASE; HUMAN LUNG-TISSUE; GENOME-WIDE ASSOCIATION; DNA METHYLATION; TGF-BETA; INFLAMMATORY PHENOTYPE; PROMOTER METHYLATION; CIGARETTE-SMOKE; PROSTATE-CANCER; FIBROBLASTS; COPD; DNA methylation; human lung fibroblasts; RNA sequencing; WGBS |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Apr 2024 13:16 |
| Last Modified: | 19 Apr 2024 13:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60905 |
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