2026-06-05T13:37:59Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/414802026-02-03T11:20:41Zcom_10630_2254col_10630_37953

00925njm 22002777a 4500 dc Reyes-Palomares, Armando author Gu, Mingxia author Grubert, Fabian author Berest, Ivan author Sa, Silin author Kasowski, Maya author Arnold, Christian author Shuai, Mao author Srivas, Rohith author Miao, Simon author Li, Dan author Snyder, Michael P. author Rabinovitch, Marlene author Zaugg, Judith B. author 2020-04 Environmental and epigenetic factors often play an important role in polygenic disorders. However, how such factors affect disease-specific tissues at the molecular level remains to be understood. Here, we address this in pulmonary arterial hypertension (PAH). We obtain pulmonary arterial endothelial cells (PAECs) from lungs of patients and controls (n = 19), and perform chromatin, transcriptomic and interaction profiling. Overall, we observe extensive remodeling at active enhancers in PAH PAECs and identify hundreds of differentially active TFs, yet find very little transcriptomic changes in steady-state. We devise a disease-specific enhancer-gene regulatory network and predict that primed enhancers in PAH PAECs are activated by the differentially active TFs, resulting in an aberrant response to endothelial signals, which could lead to disturbed angiogenesis and endothelial-to-mesenchymal-transition. We validate these predictions for a selection of target genes in PAECs stimulated with TGF-β, VEGF or serotonin. Our study highlights the role of chromatin state and enhancers in disease-relevant cell types of PAH. Reyes-Palomares, A., Gu, M., Grubert, F. et al. Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension. Nat Commun 11, 1673 (2020). https://doi.org/10.1038/s41467-020-15463-x https://hdl.handle.net/10630/41480 10.1038/s41467-020-15463-x Sistema cardiovascular - Enfermedades Epigenética Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension