Human cirrhosis: monoclonal regenerative nodules derived from hepatic progenitor cells abutting ductular reaction.
Cirrhosis is a premalignant condition leading to hepatocellular carcinoma. Cirrhotic nodules are surrounded by a rim of CK 7/CK19-positive biliary cells termed ductular reaction. Half of all regenerative cirrhotic nodules are thought to be monoclonal by studying the pattern of inactivation of the X-linked human androgen receptor gene (HUMARA). Using a new technique for lineage tracing in human liver based on the identification in the mitochondrial DNA of mutations in the cytochrome c oxidase (CCO) gene, the authors discovered that 20% of regenerative nodules were monoclonal; in addition they showed that hepatic progenitor cells within abutting CCO-deficient cells of the ductular reaction had the same mutations as the adjacent regenerative nodule, indicating a common cell origin. It is the first direct evidence that regenerative nodules in cirrhosis can be derived from hepatic progenitor cells.
Bioulac-Sage
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Service d'Anatomie Pathologique, Hôpital Pellegrin, CHU de Bordeaux, 33076 Bordeaux, France.
Balabaud
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D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D006801:Humans; D008099:Liver / Q000166:cytology; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology*; D008115:Liver Regeneration / Q000235:genetics; D009154:Mutation; D011944:Receptors, Androgen / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*
C410798:AR protein, human; D004272:DNA, Mitochondrial; D011944:Receptors, Androgen; D003576:Electron Transport Complex IV