A genetic screen reveals Foxa3 and TNFR1 as key regulators of liver repopulation.
The fundamental question of which genes are most important in controlling liver regeneration remains unanswered. We employed a parallel screen to test the impact of 43 selected genes on liver repopulation in the Fah(-/-) mouse model of hereditary tyrosinemia. We discovered that the transcription factor Foxa3 was a strong promoter of liver regeneration, while tumor necrosis factor receptor 1 (TNFR1) was the most significant suppressor of repopulation among all of the genes tested. Our approach enabled the identification of these factors as important regulators of liver repopulation and potential drug targets for the promotion of liver repopulation.
Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; Center for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
Kirk J
KJ
Wangensteen
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
Sophia
S
Zhang
Janssen Research and Development, Spring House, Pennsylvania 19477, USA.
Linda E
LE
Greenbaum
Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; Center for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; kaestner@mail.med.upenn.edu.
Klaus H
KH
Kaestner
D000818:Animals; D004195:Disease Models, Animal; D005820:Genetic Testing; D051543:Hepatocyte Nuclear Factor 3-gamma / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology; D008115:Liver Regeneration / Q000235:genetics*; D051379:Mice; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*
C496506:Foxa3 protein, mouse; D047888:Receptors, Tumor Necrosis Factor, Type I; D051543:Hepatocyte Nuclear Factor 3-gamma
Foxa3; TNFR1; injury; liver; regeneration; repopulation