TY  - JOUR
AU  - Winkler, Manuel
AU  - Staniczek, Theresa
AU  - Suhayda, Maximilian
AU  - Kürschner-Zacharias, Sina Wietje
AU  - Hoffmann, Johannes
AU  - Cordero, Julio
AU  - Kraske, Linda
AU  - Maude, Hannah
AU  - Nagy, Dorka
AU  - Manco, Rita
AU  - Sticht, Carsten
AU  - Neßling, Michelle
AU  - Richter, Karsten
AU  - Dobreva, Gergana
AU  - Randi, Anna Maria
AU  - Cebola, Inês
AU  - Schledzewski, Kai
AU  - Reiners-Koch, Philipp-Sebastian
AU  - Goerdt, Sergij
AU  - Schmid, Christian David
TI  - Endothelial c-Maf prevents MASLD-like liver fibrosis by regulating chromatin accessibility to suppress pathogenic microvascular cell subsets.
JO  - JHEP reports
VL  - 7
IS  - 9
SN  - 2589-5559
CY  - Amsterdam
PB  - Elsevier
M1  - DKFZ-2025-01679
SP  - 101475
PY  - 2025
AB  - 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
KW  - ATAC-Seq analysis (Other)
KW  - Capillarization (Other)
KW  - Cirrhosis (Other)
KW  - Liver sinusoidal endothelial cells (LSEC) (Other)
KW  - Single-cell RNA-Seq analysis (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40810103
C2  - pmc:PMC12341620
DO  - DOI:10.1016/j.jhepr.2025.101475
UR  - https://inrepo02.dkfz.de/record/303488
ER  -