Neural crest-derived cells in the liver during embryonic development and fibrogenesis

FURLAN A; AQUINO JB; ADAMEYKO I; SIERRA R; ERNFORS P

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

Cirrhosis results from repeated cycles of liver damage and scar formation. Little is known regarding the contribution of neural crest-derived cells (NCDCs) to the liver in health and disease. Previous in vitro findings likely suggest that some hepatocyte-like cells (HLCs) might be of this origin. Objective: The aim of this work was to analyze the contribution of NCDCs to the liver during development and liver fibrogenesis. Methodology: Wnt1-Cre, PLP-CreERT(2), Sox-10-CreERT(2) mice were mated with Rosa26-loxP-Tomato or Rosa26-loxP-YFP and the co-expression of the reporter gene with glial, hepatocyte and hepatic stellate cell markers was analyzed. Two models of liver fibrogenesis were generated: 1) chronic applications of thioacetamide and 2) bile duct ligation. Results: Data from in vivo studies with Wnt1-Cre:Rosa26-Tomato mice suggest a contribution of NCDCs with HLCs in the adult. For studies during embryonic stages, PLP-CreERT(2):Rosa26-YFP and Sox10-CreERT(2):Rosa26-YFP mice were used. Pregnant females were tamoxifen-injected at embryonic day 15.5 (E15.5). Numerous YFP+ cells were found at E18.5 and some of them co-expressed cytokeratin 18 and alpha-fetoprotein. None of them were desmin-. Interestingly, NCD-HLCs were anatomically distributed following a similar pattern in all strains and stages analyzed. Finally, liver fibrogenesis was found to induce a gliosis-like process and it was associated with a significant increased in numbers of HLCs. Conclusions: During normal development some HLCs could be NCD. Numbers of glial cells and HLCs increased during liver fibrogenesis,which may have implications on fibrogenesis control and on liver regeneration.