Identification of a microRNA controlling hepatic cell differentiation

The liver is mainly composed of two epithelial cell types, namely the hepatocytes and the cholangiocytes. During embryogenesis, these cells originate from hepatoblasts whose differentiation is controlled by transcriptional networks and intercellular signaling. Using in vitro and in vivo approaches, we identified miR-337-3p as a new regulator of hepatobiliary segregation. We demonstrated that miR-337-3p represses hepatocyte-specific genes while stimulating cholangiocyte-specific genes, and determined how it exerts its activity. In parallel, we searched for molecular differentiation markers that are associated with the histological differentiation grade of intrahepatic cholangiocarcinoma. We found no correlation between tumor histology and differentiation marker expression. Since histological differentiation correlates with prognosis, our results point toward necessary caution when evaluating tumor progression on the basis of histological differentiation criteria.