Liver Progenitor Cells: Cellular Origins, Plasticity, and Signaling Pathways in Liver Regeneration

The liver has a notable regenerative capacity, primarily through hepatocyte proliferation. However, when this process is impaired-due to severe and/or chronic injury-liver progenitor cells (LPCs) serve as a facultative reserve to restore hepatic function. LPCs, which are a bipotent and heterogeneous population located near the canals of Hering, can differentiate into hepatocytes and cholangiocytes. Recent evidence suggests that LPCs may originate from mature hepatic cells-such as hepatocytes, cholangiocytes, and hepatic stellate cells-through dedifferentiation under specific injury conditions. Cellular plasticity in the liver is governed by complex signaling networks that regulate LPC activation, maintenance, and lineage commitment. However, the precise cellular origin of LPCs and the mechanisms driving their activation remain incompletely defined. Therefore, this review aims to synthesize current insights into LPC biology and emphasize their diverse cellular origins, functional roles in liver regeneration, and the key signaling pathways involved. A deeper understanding of LPC dynamics may ultimately guide the development of novel therapeutic strategies to enhance liver regeneration in chronic liver disease.