Luigi Aloia obtained his PhD in 2010 from University of Naples Federico II elucidating novel regulators of embryonic stem cell pluripotency. In 2010 he joined the laboratory of Luciano Di Croce and CRG in Barcelona where he worked on epigenetic mechanisms driving the establishment of neural progenitor identity. Since 2014 he has been working as a Marie Sklodowska Curie fellow with Meritxell Huch at University of Cambridge. His research has been focused on epigenetic mechanisms governing liver regeneration.
The adult liver has exceptional regenerative potential. Upon injury, both liver epithelial cell types, cholangiocytes and hepatocytes, show significant plasticity, intended as the capacity of the cell to adopt alternative fates in response to environmental changes. Specifically, cholangiocytes have been shown to de-differentiate to a progenitor state and significantly contribute to regeneration of both epithelial cell types upon chronic liver injury or when hepatocyte response is compromised. However, the molecular mechanisms driving cholangiocyte plasticity are largely unknown. Elucidating molecular mechanisms governing regeneration is an essential step to tackle liver chronic disease, which affects 29 million people in Europe and can degenerate into cancer. We have found that the epigenetic factor TET1 is transiently up-regulated in cholangiocytes isolated upon liver injury in vivo or grown as 3D liver organoids in vitro. TET1-mediated epigenetic remodelling enables cholangiocyte plasticity regulating the expression of stem-cell and regenerative genes. Consistently, TET1 is required for the establishment of liver organoids and correct epithelial regeneration in mouse in vivo upon injury induced by a toxic diet. Moreover, reduced level of TET1 in vivo induces fibrosis upon chronic injury in mouse. Therefore, our data highlight TET1 as a key regulator of liver regeneration.