Ontology highlight
ABSTRACT:
SUBMITTER: Theodoris CV
PROVIDER: S-EPMC4359747 | biostudies-literature | 2015 Mar
REPOSITORIES: biostudies-literature
Theodoris Christina V CV Li Molong M White Mark P MP Liu Lei L He Daniel D Pollard Katherine S KS Bruneau Benoit G BG Srivastava Deepak D
Cell 20150301 6
The mechanisms by which transcription factor haploinsufficiency alters the epigenetic and transcriptional landscape in human cells to cause disease are unknown. Here, we utilized human induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) to show that heterozygous nonsense mutations in NOTCH1 that cause aortic valve calcification disrupt the epigenetic architecture, resulting in derepression of latent pro-osteogenic and -inflammatory gene networks. Hemodynamic shear stress, which ...[more]