The mammalian liver has an extraordinary regenerative capacity, capable of fully restoring its mass and function after injury or partial resection. A study led by researchers at the University of Barcelona has identified the DNA regions that activate the regeneration of this organ. The study, published in the journal Cell Genomics , provides a genome-wide map of the interactions between these regulatory elements of liver regeneration and the key genes involved in this process. The results provide a better understanding of the fundamental mechanisms of regeneration and could have future implications for the development of regenerative medicine. The paper is signed by researcher Palmira Llorens-Giralt - first author of the article - and professors Florenci Serras and Montserrat Corominas, all three from the Department of Genetics, Microbiology and Statistics of the Faculty of Biology and the Institute of Biomedicine of the UB ( IBUB ). Researchers from the Bellvitge Biomedical Research Institute (IDIBELL) and the Area CIBER of Liver and Digestive Diseases (CIBEREHD), the Centre for Genomic Regulation (CRG) and the Institute of Molecular Biology of Barcelona (IBMB-CSIC) have also participated.
The study uses mouse liver after organ resection to analyse changes in chromatin, the structure in which DNA is organized within the cell nucleus, which plays a key role in regulating gene expression during regeneration. "Resection or partial hepatectomy is a common clinical practice, both in the removal of liver tumours and in living donor transplants, where part of the liver is transplanted to a patient with liver dysfunction, so understanding how this process works can help to design strategies that optimize its response", says Montserrat Corominas, who coordinated the study.
Similarities with embryonic development of the liver
To obtain a global and dynamic view of the regeneration process, the researchers have analysed multiple genomic data that have allowed them, for example, to compare regeneration with embryonic development of the liver and to detect parallels between the two processes. With this approach, they have observed that the expression of key genes for regeneration is orchestrated by a wide variety of regeneration-responsive regulatory elements, including enhancers - DNA regions that activate gene expression - specific to regeneration, but also reactivated developmental enhancers. That is, re-used enhancers from various stages of embryonic development, with the aim of activating cellular processes essential for the proliferation of hepatocytes, the most abundant cells in the liver.
