|ZFIN ID: ZDB-PUB-190529-3|
mTORC1 Signaling is Required for the Dedifferentiation from Biliary Cell to Bi-potential Progenitor Cell in Zebrafish Liver Regeneration
He, J., Chen, J., Wei, X., Leng, H., Mu, H., Cai, P., Luo, L.
|Source:||Hepatology (Baltimore, Md.) 70(6): 2092-2106 (Journal)|
|Registered Authors:||He, Jianbo, Luo, Lingfei|
|Keywords:||mTOR, raptor, biliary epithelial cells, liver progenitor cells, proliferation|
|PubMed:||31136010 Full text @ Hepatology|
He, J., Chen, J., Wei, X., Leng, H., Mu, H., Cai, P., Luo, L. (2019) mTORC1 Signaling is Required for the Dedifferentiation from Biliary Cell to Bi-potential Progenitor Cell in Zebrafish Liver Regeneration. Hepatology (Baltimore, Md.). 70(6):2092-2106.
ABSTRACTThe liver has a high regenerative capacity. Upon 2/3 partial hepatectomy (PH), the hepatocytes proliferate and contribute to liver regeneration. After severe liver injury when the proliferation of residual hepatocytes are blocked, the biliary epithelial cells (BECs) lose their morphology and express the hepatoblast and endoderm markers, dedifferentiate into bi-potential progenitor cells (BP-PCs), then proliferate and re-differentiate into mature hepatocytes. Little is known about the mechanisms involved in the formation of BP-PCs after extreme liver injury. Using zebrafish liver extreme injury model, we found that the mTORC1 signaling regulated dedifferentiation of BECs and proliferation of BP-PCs. mTORC1 signaling was upregulated in BECs during extreme hepatocytes ablation and continuously expressed in later liver regeneration. Inhibition of mTORC1 by early chemical treatment before hepatocyte ablation blocked the dedifferentiation from BECs into BP-PCs. Late mTORC1 inhibition after liver injury reduced the proliferation of BP-PC-derived hepatocytes and BECs, but did not affect BP-PC re-differentiation. mTOR and raptor mutants exhibited defects in BEC transdifferentiation including dedifferentiation, BP-PC proliferation, and re-differentiation, similar to the chemical inhibition. CONCLUSIONS: mTORC1 signaling governs the BECs-driving liver regeneration by regulating the dedifferentiation of BECs and the proliferation of BP-PC-derived hepatocytes and BECs. This article is protected by copyright. All rights reserved.