authentic cells in their natural environment in vivo (Schwartz et al., 2014). As with the liver samples, the distinction between HLCs and primary hepatocytes was evident with respect to global gene expression profiling (Figure S3) as well as the expression of individual genes and secretion of proteins (Figure S2). Thus, our analyses confirm that neither liver samples nor HLCs faithfully reflect the cellular state of primary hepatocytes, an important limitation of eQTL/ASE studies performed with either sample type. In light of these limitations, we suggest that whole-liver eQTL studies and HLC eQTL studies should be pursued in a complementary fashion, and that functional studies should be prioritized for eGenes that are independently observed in the two types of studies, as these genes are more likely to reflect bona fide hepatocyte biology.
