Multi-modal analysis of human hepatic stellate cells identifies novel therapeutic targets for metabolic dysfunction-associated steatotic liver disease.

ABSTRACT:

Background & aims

Metabolic dysfunction-associated steatotic liver disease ranges from metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis. Transdifferentiation of hepatic stellate cells (HSCs) into fibrogenic myofibroblasts plays a critical role in the pathogenesis of MASH liver fibrosis. We compared transcriptome and chromatin accessibility of human HSCs from NORMAL, MASL, and MASH livers at single-cell resolution. We aimed to identify genes that are upregulated in activated HSCs and to determine which of these genes are key in the pathogenesis of MASH fibrosis.

Methods

Eighteen human livers were profiled using single-nucleus (sn)RNA-seq and snATAC-seq. High priority targets were identified, then

SUBMITTER: Kim HY 

PROVIDER: S-EPMC12306656 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature