Linking epigenetic regulation of liver regeneration to liver disease

Speaker

• Luigi Aloia - Laboratory for Molecular Cell Biology (LMCB) at University College London (UCL)

Abstract

The adult liver has excellent regenerative potential. After severe or persistent toxic liver injury, liver epithelial cells, hepatocytes and cholangiocytes, can de-differentiate into adult liver progenitors that restore tissue function and architecture. However, chronic damage (caused by alcohol, viruses and obesity) overwhelms liver regenerative capacity, resulting in chronic liver disease (CLD). CLD causes 2 million deaths per year worldwide and is the environment in which liver cancer arises. Thus, understanding the link between regenerative processes and liver disease is essential to identify novel therapeutic strategies for CLD and liver cancer. 

We have recently discovered that epigenetic remodelling mediated by the methylcytosine dioxygenase TET1, is required for liver regeneration by promoting the activation of adult liver progenitors after liver injury. Underlying the relevance of these epigenetic processes, reduced levels of TET1 in mouse in vivo, impair correct regeneration and induce tissue fibrosis, the most prominent sign of human CLD. Currently we are investigating how cross-talk between adult liver progenitors and the microenvironment triggers the epigenetic processes driving liver regeneration and how alterations of this cross-talk promote liver disease and cancer.