Published online Apr 27, 2019. doi: 10.4254/wjh.v11.i4.409
Peer-review started: December 19, 2018
First decision: January 16, 2019
Revised: January 23, 2019
Accepted: February 26, 2019
Article in press: February 27, 2019
Published online: April 27, 2019
A recent publication highlights the importance of high yes-associated protein (YAP) expressing cells in liver regeneration following partial hepatectomy. Although the names of the cell populations described in these articles [hybrid periportal hepatocytes (HybHP) or epithelial-mesenchymal transition (EMT)-reprogrammed hepatocytes] are not identical, they all express high levels of YAP. We hypothesize that the HybHP and EMT-reprogrammed hepatocytes might be a similar cell population. Hippo signaling is the primary pathway that regulates YAP activity. According to the contribution of these two types of cells to liver regeneration and the high YAP expression, Hippo-YAP signaling activation may be a common regulatory pathway experienced by cells undergoing dedifferentiation and reactivating proliferative activity during liver regeneration. Although no evidence has shown that HybHP cells contribute to hepatocellular carcinoma in mouse models, we can not rule out the possibility that these highly regenerative cells can further develop into tumor cells when they acquire mutations caused by viral infection or other risk factors like alcohol. The detailed mechanistic insight of the regulation of YAP expression and activity in HybHP (or other types of cells contributing to liver regeneration) is unknown. We hypothesize that liver regeneration under various conditions will eventually lead to divergent consequences, likely due to the duration of YAP activation regulated by Hippo-large tumor suppressor 1 and 2 pathway in a context- and cell type-dependent manner.
Core tip: Hybrid periportal hepatocytes (HybHP) and epithelial-mesenchymal transition-reprogrammed hepatocytes might be a similar cell population. The contribution of HybHPs to liver regeneration is associated with high expression of yes-associated protein (YAP). The detailed mechanistic insight of the regulation of YAP activity in HybHPs is undetermined. The context- and cell type-dependent regulation of Hippo- large tumor suppressor 1 and 2-YAP axes might lead to divergent consequences in liver regeneration.