Interference with the HNF4-dependent gene regulatory network diminishes endoplasmic reticulum stress in hepatocytes.

ABSTRACT:

Background

In all eukaryotic cell types, the unfolded protein response (UPR) upregulates factors that promote protein folding and misfolded protein clearance to help alleviate endoplasmic reticulum (ER) stress. Yet, ER stress in the liver is uniquely accompanied by the suppression of metabolic genes, the coordination and purpose of which are largely unknown.

Methods

Here, we combined in silico machine learning, in vivo liver-specific deletion of the master regulator of hepatocyte differentiation HNF4α, and in vitro manipulation of hepatocyte differentiation state to determine how the UPR regulates hepatocyte identity and toward what end.

Results

Machine learning identified a cluster of correlated genes that were profoundly suppressed by persistent ER stress in the liv

SUBMITTER: Shah A 

PROVIDER: S-EPMC10578741 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature