Interrogation of the Atherosclerosis-Associated <i>SORT1</i> (Sortilin 1) Locus With Primary Human Hepatocytes, Induced Pluripotent Stem Cell-Hepatocytes, and Locus-Humanized Mice

Abstract

The rs12740374 minor allele sequence enhances <i>SORT1</i> expression in hepatocytes. CRISPR-Cas9 can be used in primary human hepatocytes ex vivo and locus-humanized mice in vivo to interrogate the function of noncoding regulatory regions. Induced pluripotent stem cell-derived hepatocyte-like cells experience limitations that prevent faithful modelling of some hepatocyte expression quantitative trait loci.