Fig. 5

The roles of Notch and Wnt signaling in liver regeneration. a In hepatocyte injury models, such as the partial removal of the liver (partial hepatectomy), the liver regeneration is predominantly contributed by the proliferation of existing hepatocytes. Wnt and Notch signaling are required for hepatocyte proliferation and liver regeneration. b Following the liver injury with a biliary response or under conditions where the proliferation capacity of the hepatocyte is impaired, liver progenitor cell (LPC)-driven regeneration is an alternative mode to mediate hepatic repair. The myofibroblast-involved Notch signaling activation in LPCs guides their differentiation into cholangiocytes, whereas Wnt proteins secreted from macrophages and endothelial cells promote the differentiation of nearby LPCs into hepatocytes. The Wnt-Notch interaction during this process is mediated by Numb, a direct transcriptional target of canonical Wnt signaling that functions to inhibit Notch signaling