Researchers learn that parts of the liver expand while regeneration occurs and return to normal when regeneration ends

Researchers using digital tissue reconstruction of mouse-liver tissue have discovered what happens inside the liver when it regrows.

The liver is an organ that, when partially removed, has the ability to return to its original size, and that regeneration power is not fully understood by scientists at the moment.  This new study shows that parts of the liver expand, and one of those is the bile canalicular network. When large portions of the liver are removed and bile production goes into overdrive, a sensor called YAP moves into the nucleus to activate the HIPPO pathway to start the regeneration process.

This study was published in Molecular Systems Biology  Feb. 1.

Study authors Kirstin Meyer, Hernan Morales‐Navarrete, Sarah Seifert, Michaela Wilsch‐Braeuninger, Uta Dahmen, Elly M Tanaka, Lutz Brusch, Yannis Kalaidzidis and Marino Zerial used digital tissue reconstruction and quantitative analysis to answer the question of how cells sense the overall status of a tissue to start the regeneration process.

All of the hepatocytes are connected by the bile canalicular network. That connection is what allows tissue properties to reach each cell in the lobule, a small vascular unit  of the liver, and control the collective behavior of an organ’s cells.  

The apical-acting cytoskeleton senses the metabolic load and uses that to determine the size of an organ. Within the bile canalicular network, the apical surface of hepatocytes expands and acto-myosin contractility increases, which is sensed by YAP. During the regeneration process, the bile canalicular network of the liver returns to its normal size, and YAP returns to its location in the cytoplasm, not the nucleus of cells.

The study noted that future questions for research include the exact function of the YAP sensor and how it is controlled on a molecular level. The YAP sensor may be involved in hepatocyte differentiation, and ploidy, in addition to cell size.