High‐resolution transcriptomic and epigenetic profiling identifies novel regulators of COPD

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.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: High‐resolution transcriptomic and epigenetic profiling identifies novel regulators of COPD ; day:05 ; month:05 ; year:2023 ; extent:32 ; The EMBO journal / European Molecular Biology Organization ; (05.05.2023) (gesamt 32)

Contributors, Places and Time

• Creator: Schwartz, Uwe ; Llamazares-Prada, Maria ; Pohl, Stephanie T. ; Richter, Mandy ; Tamas, Raluca ; Schuler, Michael ; Keller, Corinna ; Mijosek, Vedrana ; Muley, Thomas ; Schneider, Marc A. ; Quast, Karsten ; Hey, Joschka ; Heußel, Claus Peter ; Warth, Arne ; Winter, Hauke ; Serçin, Özdemirhan ; Karmouty‐Quintana, Harry ; Jyothula, Soma SK ; Patel, Manish K. ; Herth, Felix ; Koch, Ina ; Petrosino, Giuseppe ; Titimeaua, Alexandru ; Mardin, Balca R. ; Weichenhan, Dieter ; Jurkowski, Tomasz P. ; Imbusch, Charles ; Brors, Benedikt ; Benes, Vladimir ; Jung, Birgit ; Wyatt, David ; Stahl, Heiko F. ; Plass, Christoph ; Jurkowska, Renata Z.

Further information

• DOI: 10.15252/embj.2022111272
• URN: urn:nbn:de:101:1-2023050515165191232887
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 10:58 AM CEST