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LIVER

Novel insights into liver homeostasis and regeneration

Nature Reviews Gastroenterology & Hepatology volume 18, pages 369–370 (2021)Cite this article

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Studies of liver regeneration after injury have provided knowledge of the role of external signals and internal metabolic and regenerative pathways. However, less is understood about homeostatic maintenance of normal liver size in the absence of external injury. Three important new studies explore liver regeneration and homeostasis using novel lineage tagging of hepatic cells and single-cell RNA transcriptomics.

Refers to Wei, Y. et al. Liver homeostasis is maintained by midlobular zone 2 hepatocytes. Science 371, eabb1625 (2021) | He, L. et al. Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair. Science 371, eabc4346 (2021) | Chembazhi, U. V. et al. Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver. Genome Res. https://doi.org/10.1101/gr.267013.120 (2021).

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References

  1. Michalopoulos, G. K. & Bhushan, B. Liver regeneration: biological and pathological mechanisms and implications. Nat. Rev. Gastroenterol. Hepatol. 18, 40–55 (2021).

    Article  Google Scholar 

  2. Font-Burgada, J. et al. Hybrid periportal hepatocytes regenerate the injured liver without giving rise to cancer. Cell 162, 766–779 (2015).

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  5. Kennedy, S., Rettinger, S., Flye, M. W. & Ponder, K. P. Experiments in transgenic mice show that hepatocytes are the source for postnatal liver growth and do not stream. Hepatology 22, 160–168 (1995).

    CAS  PubMed  Google Scholar 

  6. Wei, Y. et al. Liver homeostasis is maintained by midlobular zone 2 hepatocytes. Science 371, eabb1625 (2021).

    CAS  Article  Google Scholar 

  7. He, L. et al. Proliferation tracing reveals regional hepatocyte generation in liver homeostasis and repair. Science 371, eabc4346 (2021).

    CAS  Article  Google Scholar 

  8. Rappaport, A. M. The microcirculatory hepatic unit. Microvasc. Res. 6, 212–228 (1973).

    CAS  Article  Google Scholar 

  9. Chembazhi, U. V., Bangru, S., Hernaez, M. & Kalsotra, A. Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver. Genome Res. https://doi.org/10.1101/gr.267013.120 (2021).

    Article  PubMed  Google Scholar 

  10. Rana, B., Mischoulon, D., Xie, Y., Bucher, N. L. & Farmer, S. R. Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: reciprocal expression of C/EBP alpha and immediate-early growth response transcription factors. Mol. Cell. Biol. 14, 5858–5869 (1994).

    CAS  Article  Google Scholar 

Download references

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  1. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    George K. Michalopoulos

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  1. George K. Michalopoulos
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Correspondence to George K. Michalopoulos.

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The author declares no competing interests.

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Michalopoulos, G.K. Novel insights into liver homeostasis and regeneration. Nat Rev Gastroenterol Hepatol 18, 369–370 (2021). https://doi.org/10.1038/s41575-021-00454-0

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  • DOI: https://doi.org/10.1038/s41575-021-00454-0

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