PhD Candidate Max Planck Institute of Molecular Cell Biology and Genetics Max Planck Institute of Molecular Cell Biology and Genetics, Germany
Abstract: Tissue repair relies on the ability of cells to respond to internal and external cues, proliferate, and differentiate into functional components. The liver stands out for its remarkable regenerative capacity, driven by hepatocytes or ductal cells following injury. However, the loss of this regenerative ability and its dysregulation can lead to disease. Using an in vivo mouse models of liver regeneration, in vitro cholangiocyte organoids we had previously developed and multiple sequencing techniques, we investigated the dynamic transcriptional and epigenetic changes to the ductal epithelium after repeated liver damage. Although the liver recovered histologically and functionally, the ability of ductal cells to generate organoids declined. We identified compositional shifts in the ductal cell population, alongside with transcriptomic and epigenomic changes. Cell population and gene regulatory network analyses revealed potential mechanisms underlying ductal-driven liver regeneration. These findings lay the foundation for understanding the diminished regenerative capacity observed in chronic liver injury.
Funding Source: This research is funded by the Deutsche Forschungsgemeinschaft– 514150034 and from the European Research Council under the European Union’s Horizon Europe research and innovation programme (grant agreement No 101088869).
