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LIVER REGENERATION IN 2018

Updates on hepatic homeostasis and the many tiers of hepatobiliary repair

Deciphering the complex circuitry of liver homeostasis and repair is required to improve regenerative therapies for hepatic diseases. Studies in 2018 have identified subsets of hepatic cells that have unique reparative abilities and clarified the role of biomechanical forces and hepatobiliary reprogramming as sustainable modes of tissue repair.

Key advances

  • Rare and random TERTHigh hepatocytes in all metabolic zones of a hepatic lobule represent a distributed model of hepatic homeostasis and regeneration2.

  • Mechanosensing of altered blood flow by sinusoidal endothelial cells regulates the release of angiocrine factors that influence hepatocyte proliferation during development and regeneration5.

  • Hepatocytes and cholangiocytes can transdifferentiate into each other to aid in hepatobiliary repair when an injury is chronic or excessive and prohibits survival and proliferation of the default cell type8,9,10.

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References

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    Gilgenkrantz, H. & Collin de l’Hortet, A. Understanding liver regeneration: from mechanisms to regenerative medicine. Am. J. Pathol. 188, 1316–1327 (2018).

  2. 2.

    Lin, S. et al. Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury. Nature 556, 244–248 (2018).

  3. 3.

    Tsagianni, A. et al. Combined systemic disruption of MET and epidermal growth factor receptor signaling causes liver failure in normal mice. Am. J. Pathol. 188, 2223–2235 (2018).

  4. 4.

    Rabbany, S. Y. & Rafii, S. Blood flow forces liver growth. Nature 562, 42–43 (2018).

  5. 5.

    Lorenz, L. et al. Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival. Nature 562, 128–132 (2018).

  6. 6.

    Preziosi, M. et al. Endothelial Wnts regulate β-catenin signaling in murine liver zonation and regeneration: a sequel to the Wnt-Wnt situation. Hepatol. Commun. 2, 845–860 (2018).

  7. 7.

    Raven, A. et al. Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature 547, 350–354 (2017).

  8. 8.

    Deng, X. et al. Chronic liver injury induces conversion of biliary epithelial cells into hepatocytes. Cell Stem Cell 23, 114–122 (2018).

  9. 9.

    Russell, J. O. et al. Hepatocyte-specific β-catenin deletion during severe liver injury provokes cholangiocytes to differentiate into hepatocytes. Hepatology https://doi.org/10.1002/hep.30270 (2018).

  10. 10.

    Schaub, J. R. et al. De novo formation of the biliary system by TGFβ-mediated hepatocyte transdifferentiation. Nature 557, 247–251 (2018).

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Acknowledgements

The author’s work is supported by the NIH grants 1R01DK62277, 1R01DK116993 and R01CA204586, and the Endowed Chair for Experimental Pathology.

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Competing interests

The author declares no competing interests.

Correspondence to Satdarshan P. Monga.

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Fig. 1: Hepatic homeostasis and hepatobiliary repair.