Hepatology communications: auth.: group Herr

Hepatology communications

Segregated hepatocyte proliferation and metabolic states within the regenerating mouse liver


Shilpi Minocha, Dominic Villeneuve, Leonor Rib, Catherine Moret, Nicolas Guex, Winship Herr

  • Potential conflict of interest: Nothing to report.
  • Supported by Swiss National Science Foundation grants CRSII3_160798 (WH) and 31003A_170150 (WH) and by the University of Lausanne (WH).
  • Present address for Leonor Rib is the Bioinformatics Center, Department of Biology & Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark.


Mammalian partial hepatectomy (PH) induces an orchestrated compensatory hyperplasia, or regeneration, in remaining tissue to restore liver mass; during this process, liver functions are maintained. We probed this process in mice with feeding- and light/dark-entrained animals subjected to sham or PH surgery. Early on (i.e., 10 hours), irrespective of sham or PH surgery, hepatocytes equidistant from the portal and central veins (i.e., midlobular) accumulated the G1-phase cell-division-cycle marker cyclin D1. By 24 hours, however, cyclin D1 disappeared absent PH but was reinforced in midlobular hepatocytes after PH. At 48 hours after PH and 2 hours fasting, synchronously mitotic hepatocytes possessed less glycogen than surrounding nonproliferating hepatocytes. The differential glycogen content generated a conspicuous entangled pattern of proliferating midlobular and nonproliferating periportal and pericentral hepatocytes. The nonproliferating hepatocytes maintained aspects of normal liver properties. Conclusion: In the post-PH regenerating mouse liver, a binary switch segregates midlobular cells to proliferate side-by-side with nonproliferating periportal and pericentral cells, which maintain metabolic functions. Our results also indicate that mechanisms of liver regeneration display evolutionary flexibility. (Hepatology Communications 2017)