Yes-associated protein at the intersection of liver cell fate determination
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摘要
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 typedependent manner.
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 typedependent manner.
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 typedependent manner.
引文
1 Jiang Y,Feng D,Ma X,Fan S,Gao Y,Fu K,Wang Y,Sun J,Yao X,Liu C,Zhang H,Xu L,Liu A,Gonzalez FJ,Yang Y,Gao B,Huang M,Bi H.Pregnane X Receptor Regulates Liver Size and Liver Cell Fate by Yes-Associated Protein Activation in Mice.Hepatology 2019;69:343-358[PMID:30048004DOI:10.1002/hep.30131]
2 Font-Burgada J,Shalapour S,Ramaswamy S,Hsueh B,Rossell D,Umemura A,Taniguchi K,Nakagawa H,Valasek MA,Ye L,Kopp JL,Sander M,Carter H,Deisseroth K,Verma IM,Karin M.Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer.Cell 2015;162:766-779[PMID:26276631 DOI:10.1016/j.cell.2015.07.026]
3 Oh SH,Swiderska-Syn M,Jewell ML,Premont RT,Diehl AM.Liver regeneration requires Yap1-TGFβ-dependent epithelial-mesenchymal transition in hepatocytes.J Hepatol 2018;69:359-367[PMID:29758331 DOI:10.1016/j.jhep.2018.05.008]
4 Fitamant J,Kottakis F,Benhamouche S,Tian HS,Chuvin N,Parachoniak CA,Nagle JM,Perera RM,Lapouge M,Deshpande V,Zhu AX,Lai A,Min B,Hoshida Y,Avruch J,Sia D,Campreciós G,McClatchey AI,Llovet JM,Morrissey D,Raj L,Bardeesy N.YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC,Leading to Tumor Regression.Cell Rep 2015[PMID:25772357 DOI:10.1016/j.celrep.2015.02.027]
5 Hansen CG,Moroishi T,Guan KL.YAP and TAZ:a nexus for Hippo signaling and beyond.Trends Cell Biol 2015;25:499-513[PMID:26045258 DOI:10.1016/j.tcb.2015.05.002]
2 Font-Burgada J,Shalapour S,Ramaswamy S,Hsueh B,Rossell D,Umemura A,Taniguchi K,Nakagawa H,Valasek MA,Ye L,Kopp JL,Sander M,Carter H,Deisseroth K,Verma IM,Karin M.Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer.Cell 2015;162:766-779[PMID:26276631 DOI:10.1016/j.cell.2015.07.026]
3 Oh SH,Swiderska-Syn M,Jewell ML,Premont RT,Diehl AM.Liver regeneration requires Yap1-TGFβ-dependent epithelial-mesenchymal transition in hepatocytes.J Hepatol 2018;69:359-367[PMID:29758331 DOI:10.1016/j.jhep.2018.05.008]
4 Fitamant J,Kottakis F,Benhamouche S,Tian HS,Chuvin N,Parachoniak CA,Nagle JM,Perera RM,Lapouge M,Deshpande V,Zhu AX,Lai A,Min B,Hoshida Y,Avruch J,Sia D,Campreciós G,McClatchey AI,Llovet JM,Morrissey D,Raj L,Bardeesy N.YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC,Leading to Tumor Regression.Cell Rep 2015[PMID:25772357 DOI:10.1016/j.celrep.2015.02.027]
5 Hansen CG,Moroishi T,Guan KL.YAP and TAZ:a nexus for Hippo signaling and beyond.Trends Cell Biol 2015;25:499-513[PMID:26045258 DOI:10.1016/j.tcb.2015.05.002]