%0 Journal Article
%A Winkler, Manuel
%A Staniczek, Theresa
%A Suhayda, Maximilian
%A Kürschner-Zacharias, Sina Wietje
%A Hoffmann, Johannes
%A Cordero, Julio
%A Kraske, Linda
%A Maude, Hannah
%A Nagy, Dorka
%A Manco, Rita
%A Sticht, Carsten
%A Neßling, Michelle
%A Richter, Karsten
%A Dobreva, Gergana
%A Randi, Anna Maria
%A Cebola, Inês
%A Schledzewski, Kai
%A Reiners-Koch, Philipp-Sebastian
%A Goerdt, Sergij
%A Schmid, Christian David
%T Endothelial c-Maf prevents MASLD-like liver fibrosis by regulating chromatin accessibility to suppress pathogenic microvascular cell subsets.
%J JHEP reports
%V 7
%N 9
%@ 2589-5559
%C Amsterdam
%I Elsevier
%M DKFZ-2025-01679
%P 101475
%D 2025
%X Liver sinusoidal endothelial cells (LSECs) are highly specialized components of the hepatic vascular niche, regulating liver function and disease pathogenesis through angiocrine signaling. Recently, we identified GATA4 as a key transcription factor controlling LSEC development and protecting against liver fibrosis. As the transcription factor c-Maf was strongly downregulated in Gata4-deficient LSECs, we hypothesized that c-Maf might be an important downstream effector of GATA4 in LSEC differentiation and liver fibrogenesis.Clec4g-iCre/Maf fl/fl (Maf LSEC-KO ) mice with LSEC-specific Maf deficiency were generated and liver tissue was analyzed histologically. LSECs were isolated for bulk RNA-seq, ATAC-seq, and single-cell (sc) RNA-seq analysis. Maf LSEC-KO livers were analyzed after MASH diet feeding. The expression of MAF and its targets was analyzed in published human scRNA-seq data.Endothelial Maf deficiency resulted in perisinusoidal liver fibrosis (Sirius red 0.46
%K ATAC-Seq analysis (Other)
%K Capillarization (Other)
%K Cirrhosis (Other)
%K Liver sinusoidal endothelial cells (LSEC) (Other)
%K Single-cell RNA-Seq analysis (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40810103
%2 pmc:PMC12341620
%R 10.1016/j.jhepr.2025.101475
%U https://inrepo02.dkfz.de/record/303488