Directed differentiation of pluripotent stem cells (PSCs) into hepatocyte-like cells (HLCs) shows great promise for disease modelling as well as regenerative medicine. Unfortunately, current differentiation protocols result in heterogeneity in differentiation efficiency as well as the production of immature and undesirable cell types. In this issue (p. ), Chad Cowan and colleagues report an in-depth transcriptional and functional analysis of mature HLCs purified using the membrane marker asialoglycoprotein receptor 1 (ASGR1) from amidst the heterogeneous population of differentiating cells. The authors perform microarray profiling as well as functional assays for albumin and urea secretion and cytochrome activity, and find that the ASGR1+ cells exhibit a gene profile and functional characteristics similar to primary human hepatocytes, as compared with the HLCs negative for ASGR1. Although the cells isolated by this method are not perfect mimics of primary adult hepatocytes, the observed increase in homogeneity represents a substantial improvement in the differentiation of HLCs. This approach might therefore serve as a means to overcome the variation in the efficiency of HLC differentiation when starting from different PSC lines.
