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

• DOI: 10.15252/embj.2022111272
• Publication Date: 2023-05-05T07:34:49Z
• Authors: Uwe Schwartz; Maria Llamazares ...; Stephanie T Pohl; Mandy Richter; Raluca Tamas; Michael Schuler; Corinna Keller; Vedrana Mijosek; Thomas Muley; Marc A Schneider; Karsten Quast; Joschka Hey; Claus P Heußel; Arne Warth; Hauke Winter; Özdemirhan Serçin; Harry Karmouty‐Qu...; Soma SK Jyothula; Manish K Patel; Felix Herth; Ina Koch; Giuseppe Petrosino; Alexandru Titimeaua; Balca R Mardin; Dieter Weichenhan; Tomasz P Jurkowski; Charles D Imbusch; Benedikt Brors; Vladimir Benes; Birgit Jung; David Wyatt; Heiko F Stahl; Christoph Plass; Renata Z Jurkowska
• Keywords: CpG site; Epigenomics

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 altered epigenetic signaling in lung cells. We generated genome‐wide DNA methylation maps at single CpG resolution of primary human fibroblasts (HLFs) across stages. show the landscape is changed early COPD, changes occurring predominantly regulatory regions. RNA sequencing matched demonstrated dysregulation genes involved proliferation, repair, and extracellular matrix organization. Data integration identified 110 candidate regulators phenotypes were linked to fibroblast repair processes using phenotypic screens. Our study provides high‐resolution multi‐omic HLFs reveal novel transcriptomic signatures onset progression identify new pathogenesis diseases. The presence various factors among candidates demonstrates regulation an exciting research field holds promise therapeutic avenues patients.