Human-induced pluripotent stem cell-based hepatic modeling of lipid metabolism-associated TM6SF2-E167K variant.

ABSTRACT:

Background and aims

TM6SF2 rs58542926 (E167K) is related to an increased prevalence of metabolic dysfunction-associated steatotic liver disease. Conflicting mouse study results highlight the need for a human model to understand this mutation's impact. This study aims to create and characterize a reliable human in vitro model to mimic the effects of the TM6SF2-E167K mutation for future studies.

Approach and results

We used gene editing on human-induced pluripotent stem cells from a healthy individual to create cells with the TM6SF2-E167K mutation. After hepatocyte-directed differentiation, we observed decreased TM6SF2 protein expression, increased intracellular lipid droplets, and total cholesterol, in addition to reduced VLDL secretion. Transcriptomics revealed the upregulat

SUBMITTER: Faccioli LAP 

PROVIDER: S-EPMC11865362 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature