Figure 9. Upon low density plating, hepatocyte-like cells acquire transient mesenchymal competence within 48 h and dedifferentiate to bipotent progenitors that normally re-differentiate into hepatocyte-like cells.

A cell microenvironment enriched in Wnt signals reprograms liver progenitor cells into invasive fibrogenic myofibroblast-like cells within two weeks. These cells de novo express the cartilage gene HAPLN1 among other gene modulations. In HCCs, HAPLN1 is expressed de novo in a subset of patients presenting with HCCs that feature bad outcome, vascular invasion, high AFP serum levels and CD133+ tumor cells.