Project Details
Projekt
Deciphering the interrelation between Kupffer cells and hepatocyte polyploidization integration
Subject Area
Cell Biology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 533863915
Polyploidization of hepatocytes is a physiological process in mice and humans in which the entire genome is duplicated due to a modified cell division cycle. This polyploidization is triggered by weaning in mice, leading to tetraploid daughter cells. It is believed that the increase in cell mass and ploidy in hepatocytes is necessary to manage their substantial secretory and metabolic workload. Polyploidization can occur through a modified cell division cycle where cells successively replicate their genome without segregating chromosomes during mitosis. Mechanistically, the failure of cytokinesis leads to impaired localization of Rho A-kinase, preventing the formation of a functional contractile actomyosin ring and the ingression of the cleavage furrow. However, it remains unclear which signalling pathways in hepatocytes need to be activated or deactivated to transition from a diploid to a tetraploid state. Kupffer cells (KCs) are liver resident macrophages located in the sinusoids, constituting 15% of all liver cells. They originate from fetal precursors and self-renew within the liver. While the immunological functions of KCs are well established, a direct interrelation between KCs and hepatocyte polyploidization has not been investigated, particularly during early postnatal development. To test whether KCs interact with hepatocytes during development and contribute to the maturation and polyploidy of hepatocytes, we have developed new genetic models to deplete KCs. Using these mouse models in combination with spatial and single-cell OMICs technologies, this research proposal aims to decipher the role of KCs in generating polyploid hepatocytes and thereby investigate the function of KCs in regulating liver physiology.
DFG Programme
Research Units
