Skip to main content
SpringerLink
Log in

Hippo signaling and epithelial cell plasticity in mammalian liver development, homeostasis, injury and disease

  • Review
  • SCLS-CBIS Joint Life Science Research Workshop
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

A traditional view of cellular differentiation is unidirectional: progenitor cells adopt specific fates in response to environmental cues resulting in deployment of cell-specific gene expression programs and acquisition of unique differentiated cellular properties such as production of structural and functional proteins that define individual cell types. In both development and in tissue repair stem and progenitor cells are thought to both self-renew to maintain the pool of precursors and to expand to give rise to transient amplifying and differentiated cell types. Recently, however, it has become appreciated that differentiated cell types can be reprogrammed to adopt progenitor and stem cell properties. In the case of epithelial cells in the mammalian liver, hepatocytes and biliary epithelial cells there is a significant degree of plasticity between these lineages that has been implicated in mechanisms of tissue repair and in liver pathologies such as cancer. Recent studies have highlighted the role of Hippo signaling, an emerging growth control and tumor suppressor pathway, in regulating epithelial cell plasticity in the mammalian liver and in this review, the role of cellular plasticity and Hippo signaling in regulating normal and abnormal tissue responses in the mammalian liver will be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alder, O., Cullum, R., Lee, S., Kan, A.C., Wei, W., Yi, Y., Garside, V.C., Bilenky, M., Griffith, M., Morrissy, A.S., et al. (2014). Hippo signaling influences HNF4A and FOXA2 enhancer switching during hepatocyte differentiation. Cell Rep 9, 261–271.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ally, A., Balasundaram, M., Carlsen, R., Chuah, E., Clarke, A., Dhalla, N., Holt, R.A., Jones, S.J.M., Lee, D., Ma, Y., et al. (2017). Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell 169, 1327–1341.e23.

    Google Scholar 

  • Alwahsh, S.M., Rashidi, H., and Hay, D.C. (2018). Liver cell therapy: is this the end of the beginning? Cell Mol Life Sci 75, 1307–1324.

    CAS  PubMed  Google Scholar 

  • Bai, H., Zhang, N., Xu, Y., Chen, Q., Khan, M., Potter, J.J., Nayar, S.K., Cornish, T., Alpini, G., Bronk, S., et al. (2012). Yes-associated protein regulates the hepatic response after bile duct ligation. Hepatology 56, 1097–1107.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cai, W.Y., Lin, L.Y., Hao, H., Zhang, S.M., Ma, F., Hong, X.X., Zhang, H., Liu, Q.F., Ye, G.D., Sun, G.B., et al. (2017). Yes-associated protein/TEA domain family member and hepatocyte nuclear factor 4-alpha (HNF4α) repress reciprocally to regulate hepatocarcinogenesis in rats and mice. Hepatology 65, 1206–1221.

    CAS  PubMed  Google Scholar 

  • Chen, J., Chen, L., Zern, M.A., Theise, N.D., Diehl, A.M., Liu, P., and Duan, Y. (2017). The diversity and plasticity of adult hepatic progenitor cells and their niche. Liver international: official journal of the International Association for the Study of the Liver 37, 1260–1271.

    Google Scholar 

  • Choi, T.Y., Ninov, N., Stainier, D.Y.R., and Shin, D. (2014). Extensive conversion of hepatic biliary epithelial cells to hepatocytes after near total loss of hepatocytes in zebrafish. Gastroenterology 146, 776–788.

    CAS  PubMed  Google Scholar 

  • Dorrell, C., Erker, L., Schug, J., Kopp, J.L., Canaday, P.S., Fox, A.J., Smirnova, O., Duncan, A.W., Finegold, M.J., Sander, M., et al. (2011). Prospective isolation of a bipotential clonogenic liver progenitor cell in adult mice. Genes Dev 25, 1193–1203.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Duncan, A.W., Dorrell, C., and Grompe, M. (2009). Stem cells and liver regeneration. Gastroenterology 137, 466–481.

    PubMed  PubMed Central  Google Scholar 

  • Español-Suñer, R., Carpentier, R., Van Hul, N., Legry, V., Achouri, Y., Cordi, S., Jacquemin, P., Lemaigre, F., and Leclercq, I.A. (2012). Liver progenitor cells yield functional hepatocytes in response to chronic liver injury in mice. Gastroenterology 143, 1564–1575.e7.

    PubMed  Google Scholar 

  • Fan, B., Malato, Y., Calvisi, D.F., Naqvi, S., Razumilava, N., Ribback, S., Gores, G.J., Dombrowski, F., Evert, M., Chen, X., et al. (2012). Cholangiocarcinomas can originate from hepatocytes in mice. J Clin Invest 122, 2911–2915.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fausto, N. (2004). Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells. Hepatology 39, 1477–1487.

    PubMed  Google Scholar 

  • Font-Burgada, J., Shalapour, S., Ramaswamy, S., Hsueh, B., Rossell, D., Umemura, A., Taniguchi, K., Nakagawa, H., Valasek, M.A., Ye, L., et al. (2015). Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer. Cell 162, 766–779.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Furuyama, K., Kawaguchi, Y., Akiyama, H., Horiguchi, M., Kodama, S., Kuhara, T., Hosokawa, S., Elbahrawy, A., Soeda, T., Koizumi, M., et al. (2011). Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet 43, 34–41.

    CAS  PubMed  Google Scholar 

  • Grijalva, J.L., Huizenga, M., Mueller, K., Rodriguez, S., Brazzo, J., Camargo, F., Sadri- Vakili, G., and Vakili, K. (2014). Dynamic alterations in Hippo signaling pathway and YAP activation during liver regeneration. Am J Physiol-Gastrointestinal Liver Physiol 307, G196–G204.

    CAS  Google Scholar 

  • Guest, R.V., Boulter, L., Kendall, T.J., Minnis- Lyons, S.E., Walker, R., Wigmore, S.J., Sansom, O.J., and Forbes, S.J. (2014). Cell lineage tracing reveals a biliary origin of intrahepatic cholangiocarcinoma. Cancer Res 74, 1005–1010.

    CAS  PubMed  Google Scholar 

  • Guo, X., Zhao, Y., Yan, H., Yang, Y., Shen, S., Dai, X., Ji, X., Ji, F., Gong, X.G., Li, L., et al. (2017). Single tumor-initiating cells evade immune clearance by recruiting type II macrophages. Genes Dev 31, 247–259.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Halder, G., and Johnson, R.L. (2011). Hippo signaling: growth control and beyond. Development 138, 9–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  • He, J., Lu, H., Zou, Q., and Luo, L. (2014). Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary transdifferentiation in zebrafish. Gastroenterology 146, 789–800.e8.

    CAS  PubMed  Google Scholar 

  • Holczbauer, Á., Factor, V.M., Andersen, J.B., Marquardt, J.U., Kleiner, D. E., Raggi, C., Kitade, M., Seo, D., Akita, H., Durkin, M.E., et al. (2013). Modeling pathogenesis of primary liver cancer in lineage-specific mouse cell types. Gastroenterology 145, 221–231.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M.M.A., Ellis, E., van Wenum, M., Fuchs, S.A., de Ligt, J., et al. (2015). Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160, 299–312.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jörs, S., Jeliazkova, P., Ringelhan, M., Thalhammer, J., Dürl, S., Ferrer, J., Sander, M., Heikenwalder, M., Schmid, R.M., Siveke, J.T., et al. (2015). Lineage fate of ductular reactions in liver injury and carcinogenesis. J Clin Invest 125, 2445–2457.

    PubMed  PubMed Central  Google Scholar 

  • Katsuda, T., Kawamata, M., Hagiwara, K., Takahashi, R.U., Yamamoto, Y., Camargo, F.D., and Ochiya, T. (2017). Conversion of terminally committed hepatocytes to culturable bipotent progenitor cells with regenerative capacity. Cell Stem Cell 20, 41–55.

    CAS  PubMed  Google Scholar 

  • Kim, W., Khan, S.K., Liu, Y., Xu, R., Park, O., He, Y., Cha, B., Gao, B., and Yang, Y. (2018). Hepatic Hippo signaling inhibits protumoural microenvironment to suppress hepatocellular carcinoma. Gut 67, 1692–1703.

    CAS  PubMed  Google Scholar 

  • Kopp, J.L., Grompe, M., and Sander, M. (2016). Stem cells versus plasticity in liver and pancreas regeneration. Nat Cell Biol 18, 238–245.

    PubMed  Google Scholar 

  • Krenkel, O., and Tacke, F. (2017). Liver macrophages in tissue homeostasis and disease. Nat Rev Immunol 17, 306–321.

    CAS  PubMed  Google Scholar 

  • Kubes, P., and Jenne, C. (2018). Immune responses in the liver. Annu Rev Immunol 36, 247–277.

    CAS  PubMed  Google Scholar 

  • Lee, D.H., Park, J.O., Kim, T.S., Kim, S.K., Kim, T.H., Kim, M.C., Park, G.S., Kim, J.H., Kuninaka, S., Olson, E.N., et al. (2016). LATS-YAP/TAZ controls lineage specification by regulating TGFβ signaling and Hnf4α expression during liver development. Nat Commun 7, 11961.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, K.P., Lee, J.H., Kim, T.S., Kim, T.H., Park, H.D., Byun, J.S., Kim, M. C., Jeong, W.I., Calvisi, D.F., Kim, J.M., et al. (2010). The HippoSalvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc Natl Acad Sci USA 107, 8248–8253.

    CAS  PubMed  Google Scholar 

  • Lemoinne, S., Thabut, D., and Housset, C. (2016). Portal myofibroblasts connect angiogenesis and fibrosis in liver. Cell Tissue Res 365, 583–589.

    CAS  PubMed  Google Scholar 

  • Lin, S., Nascimento, E.M., Gajera, C.R., Chen, L., Neuhöfer, P., Garbuzov, A., Wang, S., and Artandi, S.E. (2018). Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury. Nature 556, 244–248.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Llovet, J.M., Zucman- Rossi, J., Pikarsky, E., Sangro, B., Schwartz, M., Sherman, M., and Gores, G. (2016). Hepatocellular carcinoma. Nat Rev Dis Primers 2, 16018.

    PubMed  Google Scholar 

  • Lu, L., Finegold, M.J., and Johnson, R.L. (2018). Hippo pathway coactivators Yap and Taz are required to coordinate mammalian liver regeneration. Exp Mol Med 50, e423.

    PubMed  PubMed Central  Google Scholar 

  • Lu, L., Li, Y., Kim, S.M., Bossuyt, W., Liu, P., Qiu, Q., Wang, Y., Halder, G., Finegold, M.J., Lee, J.S., et al. (2010). Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver. Proc Natl Acad Sci USA 107, 1437–1442.

    CAS  PubMed  Google Scholar 

  • Lu, W.Y., Bird, T.G., Boulter, L., Tsuchiya, A., Cole, A.M., Hay, T., Guest, R.V., Wojtacha, D., Man, T.Y., Mackinnon, A., et al. (2015). Hepatic progenitor cells of biliary origin with liver repopulation capacity. Nat Cell Biol 17, 971–983.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Machado, M.V., Michelotti, G.A., Pereira, T.A., Xie, G., Premont, R., Cortez- Pinto, H., and Diehl, A.M. (2015). Accumulation of duct cells with activated YAP parallels fibrosis progression in non-alcoholic fatty liver disease. J Hepatol 63, 962–970.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Malato, Y., Naqvi, S., Schürmann, N., Ng, R., Wang, B., Zape, J., Kay, M. A., Grimm, D., and Willenbring, H. (2011). Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration. J Clin Invest 121, 4850–4860.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marquardt, J.U., Andersen, J.B., and Thorgeirsson, S.S. (2015). Functional and genetic deconstruction of the cellular origin in liver cancer. Nat Rev Cancer 15, 653–667.

    CAS  PubMed  Google Scholar 

  • Michalopoulos, G.K. (2017). Hepatostat: Liver regeneration and normal liver tissue maintenance. Hepatology 65, 1384–1392.

    PubMed  Google Scholar 

  • Michalopoulos, G.K., and DeFrances, M.C. (1997). Liver regeneration. Science 276, 60–66.

    CAS  PubMed  Google Scholar 

  • Mu, X., Español-Suñer, R., Mederacke, I., Affò, S., Manco, R., Sempoux, C., Lemaigre, F.P., Adili, A., Yuan, D., Weber, A., et al. (2015). Hepatocellular carcinoma originates from hepatocytes and not from the progenitor/biliary compartment. J Clin Invest 125, 3891–3903.

    PubMed  PubMed Central  Google Scholar 

  • Ober, E.A., and Lemaigre, F.P. (2018). Development of the liver: insights into organ and tissue morphogenesis. J Hepatol 68, 1049–1062.

    CAS  PubMed  Google Scholar 

  • Pan, D. (2010). The Hippo signaling pathway in development and cancer. Dev Cell 19, 491–505.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Patel, S.H., Camargo, F.D., and Yimlamai, D. (2017). Hippo signaling in the liver regulates organ size, cell fate, and carcinogenesis. Gastroenterology 152, 533–545.

    CAS  PubMed  Google Scholar 

  • Poisson, J., Lemoinne, S., Boulanger, C., Durand, F., Moreau, R., Valla, D., and Rautou, P.E. (2017). Liver sinusoidal endothelial cells: Physiology and role in liver diseases. J Hepatol 66, 212–227.

    CAS  PubMed  Google Scholar 

  • Raven, A., Lu, W.Y., Man, T.Y., Ferreira- Gonzalez, S., O’ Duibhir, E., Dwyer, B.J., Thomson, J.P., Meehan, R.R., Bogorad, R., Koteliansky, V., et al. (2017). Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature 547, 350–354.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schaub, J.R., Malato, Y., Gormond, C., and Willenbring, H. (2014). Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury. Cell Rep 8, 933–939.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schaub, J.R., Huppert, K.A., Kurial, S.N.T., Hsu, B.Y., Cast, A.E., Donnelly, B., Karns, R.A., Chen, F., Rezvani, M., Luu, H.Y., et al. (2018). De novo formation of the biliary system by TGFβ-mediated hepatocyte transdifferentiation. Nature 557, 247–251.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sekiya, S., and Suzuki, A. (2012). Intrahepatic cholangiocarcinoma can arise from Notch-mediated conversion of hepatocytes. J Clin Invest 122, 3914–3918.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shin, S., Walton, G., Aoki, R., Brondell, K., Schug, J., Fox, A., Smirnova, O., Dorrell, C., Erker, L., Chu, A.S., et al. (2011). Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential. Genes Dev 25, 1185–1192.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shin, S., Wangensteen, K.J., Teta- Bissett, M., Wang, Y.J., Mosleh- Shirazi, E., Buza, E.L., Greenbaum, L.E., and Kaestner, K.H. (2016). Genetic lineage tracing analysis of the cell of origin of hepatotoxin-induced liver tumors in mice. Hepatology 64, 1163–1177.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Si-Tayeb, K., Lemaigre, F.P., and Duncan, S.A. (2010). Organogenesis and development of the liver. Dev Cell 18, 175–189.

    CAS  PubMed  Google Scholar 

  • Stanger, B.Z. (2015). Cellular homeostasis and repair in the mammalian liver. Annu Rev Physiol 77, 179–200.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Suzuki, A., Sekiya, S., Onishi, M., Oshima, N., Kiyonari, H., Nakauchi, H., and Taniguchi, H. (2008). Flow cytometric isolation and clonal identification of self-renewing bipotent hepatic progenitor cells in adult mouse liver. Hepatology 48, 1964–1978.

    CAS  PubMed  Google Scholar 

  • Tanaka, M., and Iwakiri, Y. (2016). The hepatic lymphatic vascular system: structure, function, markers, and lymphangiogenesis. Cell Mol Gastroenterol Hepatol 2, 733–749.

    PubMed  PubMed Central  Google Scholar 

  • Tarlow, B.D., Finegold, M.J., and Grompe, M. (2014a). Clonal tracing of Sox9+ liver progenitors in mouse oval cell injury. Hepatology 60, 278–289.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tarlow, B.D., Pelz, C., Naugler, W.E., Wakefield, L., Wilson, E.M., Finegold, M.J., and Grompe, M. (2014b). Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes. Cell Stem Cell 15, 605–618.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Theise, N.D., Saxena, R., Portmann, B.C., Thung, S.N., Yee, H., Chiriboga, L., Kumar, A., and Crawford, J.M. (1999). The canals of Hering and hepatic stem cells in humans. Hepatology 30, 1425–1433.

    CAS  PubMed  Google Scholar 

  • Tolosa, L., Pareja, E., and Gomez-Lechon, M.J. (2016). Clinical application of pluripotent stem cells: an alternative cell-based therapy for treating liver diseases? Transplantation 100, 2548–2557.

    CAS  PubMed  Google Scholar 

  • Tschaharganeh, D.F., Xue, W., Calvisi, D.F., Evert, M., Michurina, T.V., Dow, L.E., Banito, A., Katz, S.F., Kastenhuber, E.R., Weissmueller, S., et al. (2016). p53-Dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer. Cell 165, 1546–1547.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tsuchida, T., and Friedman, S.L. (2017). Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol 14, 397–411.

    CAS  PubMed  Google Scholar 

  • Wang, B., Zhao, L., Fish, M., Logan, C.Y., and Nusse, R. (2015). Self-renewing diploid Axin2+ cells fuel homeostatic renewal of the liver. Nature 524, 180–185.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, X., Foster, M., Al- Dhalimy, M., Lagasse, E., Finegold, M., and Grompe, M. (2003). The origin and liver repopulating capacity of murine oval cells. Proc Natl Acad Sci USA 100(Suppl 1), 11881–11888.

    Google Scholar 

  • Wang, X., Zheng, Z., Caviglia, J.M., Corey, K.E., Herfel, T.M., Cai, B., Masia, R., Chung, R.T., Lefkowitch, J.H., Schwabe, R.F., et al. (2016). Hepatocyte TAZ/WWTR1 promotes inflammation and fibrosis in nonalcoholic steatohepatitis. Cell Metab 24, 848–862.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu, H., Zhou, X., Fu, G.B., He, Z.Y., Wu, H.P., You, P., Ashton, C., Wang, X., Wang, H.Y., and Yan, H.X. (2017). Reversible transition between hepatocytes and liver progenitors for in vitro hepatocyte expansion. Cell Res 27, 709–712.

    PubMed  PubMed Central  Google Scholar 

  • Xu, M.Z., Yao, T.J., Lee, N.P.Y., Ng, I.O.L., Chan, Y.T., Zender, L., Lowe, S.W., Poon, R.T.P., and Luk, J.M. (2009). Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer 115, 4576–4585.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, L., Wang, W.H., Qiu, W.L., Guo, Z., Bi, E., and Xu, C.R. (2017). A single-cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation. Hepatology 66, 1387–1401.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yanger, K., Knigin, D., Zong, Y., Maggs, L., Gu, G., Akiyama, H., Pikarsky, E., and Stanger, B.Z. (2014). Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. Cell Stem Cell 15, 340–349.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yanger, K., and Stanger, B.Z. (2011). Facultative stem cells in liver and pancreas: fact and fancy. Dev Dyn 240, 521–529.

    PubMed  PubMed Central  Google Scholar 

  • Yanger, K., Zong, Y., Maggs, L.R., Shapira, S.N., Maddipati, R., Aiello, N. M., Thung, S.N., Wells, R.G., Greenbaum, L.E., and Stanger, B.Z. (2013). Robust cellular reprogramming occurs spontaneously during liver regeneration. Genes Dev 27, 719–724.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yi, J., Lu, L., Yanger, K., Wang, W., Sohn, B.H., Stanger, B.Z., Zhang, M., Martin, J.F., Ajani, J.A., Chen, J., et al. (2016). Large tumor suppressor homologs 1 and 2 regulate mouse liver progenitor cell proliferation and maturation through antagonism of the coactivators YAP and TAZ. Hepatology 64, 1757–1772.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yimlamai, D., Christodoulou, C., Galli, G.G., Yanger, K., Pepe- Mooney, B., Gurung, B., Shrestha, K., Cahan, P., Stanger, B.Z., and Camargo, F. D. (2014). Hippo pathway activity influences liver cell fate. Cell 157, 1324–1338.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yoo, K.S., Lim, W.T., and Choi, H.S. (2016). Biology of cholangiocytes: from bench to bedside. Gut Liver 10, 687–698.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yovchev, M., Jaber, F.L., Lu, Z., Patel, S., Locker, J., Rogler, L.E., Murray, J.W., Sudol, M., Dabeva, M.D., Zhu, L., et al. (2016). Experimental model for successful liver cell therapy by Lenti TTR-YapERT2 transduced hepatocytes with tamoxifen control of Yap subcellular location. Sci Rep 6, 19275.

    Google Scholar 

  • Zajicek, G., Oren, R., and Weinreb Jr., M. (1985). The streaming liver. Liver 5, 293–300.

    CAS  PubMed  Google Scholar 

  • Zhang, T., Zhang, J., You, X., Liu, Q., Du, Y., Gao, Y., Shan, C., Kong, G., Wang, Y., Yang, X., et al. (2012). Hepatitis B virus X protein modulates oncogene Yes-associated protein by CREB to promote growth of hepatoma cells. Hepatology 56, 2051–2059.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Cancer Prevention and Research Institute of Texas (CPRIT) Award RP180530.

Author information

Authors and Affiliations

  1. Department of Cancer Biology, University of Texas, MD Anderson Cancer Center, 6767 Bertner Ave, Houston, TX, 77030, USA

    Randy L. Johnson

Authors
  1. Randy L. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Randy L. Johnson.

Ethics declarations

Compliance and ethics The author(s) declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Johnson, R.L. Hippo signaling and epithelial cell plasticity in mammalian liver development, homeostasis, injury and disease. Sci. China Life Sci. 62, 1609–1616 (2019). https://doi.org/10.1007/s11427-018-9510-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-018-9510-3

Keywords

Search

Navigation