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Regulation of hepatocyte identity and quiescence

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Abstract

The liver is a highly differentiated organ with a central role in metabolism, detoxification and systemic homeostasis. To perform its multiple tasks, liver parenchymal cells, the hepatocytes, express a large complement of enabling genes defining their complex phenotype. This phenotype is progressively acquired during fetal development and needs to be maintained in adulthood to guarantee the individual’s survival. Upon injury or loss of functional mass, the liver displays an extraordinary regenerative response, mainly based on the proliferation of hepatocytes which otherwise are long-lived quiescent cells. Increasing observations suggest that loss of hepatocellular differentiation and quiescence underlie liver malfunction in chronic liver disease and pave the way for hepatocellular carcinoma development. Here, we briefly review the essential mechanisms leading to the acquisition of liver maturity. We also identify the key molecular factors involved in the preservation of hepatocellular homeostasis and finally discuss potential strategies to preserve liver identity and function.

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Acknowledgments

The work in the authors’ laboratory was funded by CIBEREHD, FIS PI10/02642, PI13/00359, PI10/00038 and PI13/00385, all from Instituto de Salud Carlos III (ISCIII) and co-financed by “Fondo Europeo de Desarrollo Regional” (FEDER) “Una manera de hacer Europa”.We thank all the current and past members of our laboratory.

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  1. Division of Hepatology, CIMA, University of Navarra, CIBEREHD, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Avda. Pio XII, n55, 31008, Pamplona, Spain

    Carmen Berasain & Matías A. Avila

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  1. Carmen Berasain
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  2. Matías A. Avila
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Correspondence to Carmen Berasain or Matías A. Avila.

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Berasain, C., Avila, M.A. Regulation of hepatocyte identity and quiescence. Cell. Mol. Life Sci. 72, 3831–3851 (2015). https://doi.org/10.1007/s00018-015-1970-7

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  • DOI: https://doi.org/10.1007/s00018-015-1970-7

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