Abstract
Abstract Graphene quantum dots (GQDs) have been found to promote the efficient differentiation of stem cells into a variety of cell types. However, their bioactivity and signaling mechanisms in the hepatic lineage have not been fully investigated. Here, we report that the hepatoblast (HB) differentiation rate can be promoted by using Ca 2+ -rich coffee bean (CB)-derived GQDs, where the incorporated calcium ions activate the signaling of insulin-like growth factor 1 receptor (IGF1R)-protein kinase B (AKT). We also found that the human pluripotent stem cell (hPSC)-derived HBs from the CB-GQD treatment tend to upregulate the maturation into hepatocyte-like cells and downregulate the differentiation towards cholangiocytes, thereby successfully obtaining a large number of functional hepatocyte-like cells. Moreover, the activation of IGF1R from the CB-GQD treatment enhances the HB differentiation efficiency regardless of growth factors, implying that chelated calcium may play a key role in activating IGF1R. Our findings suggest that CB-GQDs with independent bioactivity can be widely used in place of IGF1 and represent a cost-effective growth factor as well as a potential differentiation factor.