Hepatoblast-like cells populate the adult p53 knockout mouse liver: evidence for a hyperproliferative maturation-arrested stem cell compartment.
Although p53 regulates the cell cycle and apoptosis, gross embryonic development is normal in the p53 knockout (-/-) mouse. In this study, we comprehensively assessed liver development in p53 -/- mice (from embryonic day 15 to adult) for evidence of a cell cycle-induced perturbation in differentiation. Liver cell proliferation in the embryo and newborn is similar in p53 -/- and +/+ mice; in contrast, -/- adult hepatocytes divide at twice the rate of wild types. Developmental expression patterns of liver-specific markers that are up-regulated (e.g., phosphoenolpyruvate carboxykinase and aldolase B) and down-regulated (e.g., alpha-fetoprotein) are similar. Therefore, embryonic and perinatal liver development is normal in the absence of p53. However, the p53 -/- adult liver displays small blast-like cells, the majority being hepatic and some lymphoid. These cells appear in periportal regions and can infiltrate the parenchyma. The hepatic blast-like cells express both mature and immature liver markers, suggesting that differentiation of the liver stem cell compartment is blocked.
Dumble
M L
ML
Department of Biochemistry, The University of Western Australia, Crawley 6009, Western Australia, Australia.
Knight
B
B
Quail
E A
EA
Yeoh
G C
GC
D000818:Animals; D017209:Apoptosis; D001491:Basophils / Q000166:cytology; D015415:Biomarkers; D002452:Cell Count; D002454:Cell Differentiation; D002455:Cell Division; D022781:Hepatocytes / Q000166:cytology; D008099:Liver / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D013234:Stem Cells / Q000166:cytology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
D015415:Biomarkers; D016159:Tumor Suppressor Protein p53