Characteristics of Hepatic Progenitor Cells During Liver Development and Regeneration

Liver is the largest organ in the body and performs the important function of maintaining homeostasis. The liver parenchymal cells, hepatocytes, and cholangiocytes originate from the hepatic progenitor cells. Hepatic progenitor cells proliferate in the early liver bud, derived from the foregut endoderm during the mid-fetal liver stage, and differentiate into mature cells in the late-fetal and postnatal liver. The liver non-parenchymal cells such as the stellate cells, portal fibroblasts, sinusoidal endothelial cells, and Kupffer cells are considered important for the proliferation and differentiation of hepatic progenitor cells. Our group recently established a new colony forming assay system that involved co-culturing with mesenchymal cells and studied the mechanisms regulating the characteristics of the hepatic progenitor cells. The MEK-ERK signaling pathway is usually involved in the progression of the cell cycle. However, high activation of MEK-ERK signal suppresses long-term proliferation of hepatic progenitor cells through the induction of p16/19cdkn2a. In addition, a new stem/progenitor cell marker, brain expressed X-linked 2 (Bex2), has been defined using knock-in mouse model and our co-culture system. Bex2 is expressed in the progenitor cell fraction, in both fetal and adult injured livers. In this review, we discuss about the characteristics of liver progenitor cells during embryonic development and liver regeneration.