The liver is known as an organ with high proliferation potential. Clarifying the cellular origin and deepening the understanding of liver regeneration mechanisms will help provide new directions for the treatment of liver disease. With the development and application of lineage tracing technology, the specific distribution and dynamic changes of hepatocyte subpopulations in homeostasis and liver injury have been illustrated. Self-replication of hepatocytes is responsible for the maintenance of liver function and mass under homeostasis. The compensatory proliferation of remaining hepatocytes is the main mechanism of liver regeneration following acute and chronic liver injury. Transdifferentiation between hepatocytes and cholangiocytes has been recognized upon severe chronic liver injury. Wnt/β-catenin, Hippo/YAP and Notch signalling play essential roles in the maintenance of homeostatic liver and hepatocyte-to-cholangiocyte conversion under liver injury. In this review, we summarized the recent studies on cell origin of newly generated hepatocytes and the underlying mechanisms of liver regeneration in homeostasis and liver injury.
Keywords: ScRNA-seq; cholangiocytes; compensatory proliferation; hepatocyte regeneration; hepatocyte subpopulation; lineage tracing; liver progenitor cells; metabolic zonation; transdifferentiation.
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