Molecular Mechanisms Regulating the Proliferation and Maturation of Hepatic Progenitor Cells During Liver Development

Abstract The liver is the central organ regulating homeostatic processes such as detoxification, amino acid and lipid metabolism, and serum protein expression. For these adult liver functions, the liver parenchymal cells or hepatocytes express many metabolic and functional genes. In contrast, the fetal liver has few metabolic functions but supports hematopoietic cell proliferation during embryonic development. The molecular mechanisms regulating the maturation of fetal hepatic progenitor cells into functional hepatocytes are studied and several soluble factors such as oncostatin M are associated with this maturation step. Recently, we found a helix-loop-helix transcriptional factor, Mist1, inducing hepatic progenitor cell maturation in vitro. Increased activation of the MEK-MAP kinase pathway is also involved in the cell cycle arrest of hepatic progenitor cells. This chapter discusses these molecular mechanisms regulating the proliferation and differentiation of hepatic progenitor cells.