The generation of mature cell types from pluripotent stem cells (PSCs) relies on lineage-specific markers to track and enrich for distinct cell populations. During hepatocyte differentiation, the induction of the definitive endoderm is a crucial step; however, to date there are no markers that exclusively recognise differentiating human endoderm, nor any that can select for hepatocyte-fated cells from within this population. Now, on p. , Gordon Keller and colleagues report on the identification of two antibodies that can be used to identify and select for cells undergoing human endoderm differentiation from PSCs. The authors name the antibodies HDE1, which exclusively marks the entire endoderm population as it emerges, and HDE2, which marks emerging hepatic progenitors and mature hepatocytes. The authors show that the extent of HDE1 reactivity correlates with hepatic potential, and, importantly, that the two antibodies work across numerous different human PSC lines. This exciting breakthrough enables the individual monitoring of both endoderm induction and hepatic specification, leading to a more efficient protocol for directed differentiation of human hepatocytes from PSCs.
