Understanding the molecular mechanisms of adult liver regeneration. (360G-Wellcome-104151_Z_14_Z)

In the intestine and stomach, organs with extensive self-renewal, Lgr5 marks adult stem cell populations that are constantly cycling. In the liver, an organ with limited cellular turnover but huge regenerative capacity, Lgr5 is not detected under physiological conditions. However, marks a new stem/progenitor cell population that gets activated upon damage and contributes to restore the tissue and reinstall homeostasis. The main goal of this proposal is to understand the molecular mechanisms, t hat following tissue damage, regulates the transition of adult liver cells from a quiescent to an activated state, from the role of the niche during this transition to the epigenetic changes triggering this activation. The main focus of this research plan will be: Plan1) Identify the quiescent cell/s that become activated cells during damage-regeneration; Plan2) Elucidate the niche for activated stem cells; Plan3) Identify the gene regulation mechanisms (epigenetic) involved in liver stem cell activation following damage. As liver disease and liver cancer are highly associated to liver damage, understanding the mechanism regulating stem cell activation holds promise to extend our knowledge not only of liver regeneration but also of liver disease and cancer.