In addition, other evidence suggests that hepatocytes are capable of lineage conversion, acting as precursors of biliary epithelial cells during biliary injury. To test these concepts, we generated a hepatocyte fate-tracing model based on timed and specific Cre recombinase expression and marker

gene activation in all hepatocytes of adult Rosa26 reporter mice with an adenoassociated viral (AAV) vector. We found that newly formed hepatocytes derived from preexisting hepatocytes in the normal liver and that liver progenitor cells contributed minimally to acute hepatocyte regeneration. Further, we found no evidence that biliary injury induced conversion of hepatocytes into biliary epithelial cells. These results therefore restore the previously prevailing paradigms of Midostaurin liver homeostasis and regeneration. In addition, our new vector system will be a valuable tool for timed, efficient,

and specific loop out of floxed sequences in hepatocytes. Few phenomena have attracted the attention of tissue biologists as has the capacity of liver to regenerate. There are several intriguing aspects of this phenomenon, of which perhaps the most important is that the regenerated liver returns to almost exactly 100% of the original liver weight, as though governed by a “hepatostat.”1-3 Tissue damage leading to loss of liver is usually either diffuse (viruses, etc.) or localized to specific areas of the hepatic lobule, most commonly in the centrilobular region (chemicals requiring metabolic activation, such as acetaminophen, etc.). In order to distinguish between phenomena find more truly related to regeneration and those MCE公司 related to the inflammatory response due to hepatocyte necrosis, liver regeneration after partial hepatectomy has been a very popular model with investigators

to study liver regeneration. It is generally accepted that following hepatectomy, hepatocytes, biliary cells, stellate cells, Kupffer cells, and endothelial cells replicate to make more of their own type. It has been argued, however, that liver regeneration after partial hepatectomy may unduly emphasize the capacity of the cells of the liver to take care of their own regeneration, entering into proliferation and replacing the lost cell type with phenotypic fidelity. In the last three decades, however, reproducible experimental models have been developed in which proliferation of hepatocytes during regeneration is suppressed.4, 5 Under those circumstances, a population of cells coming under the names of “oval” or “progenitor” cells emerge in the periportal areas, expand within the lobule, and eventually differentiate to become hepatocytes. Several studies have argued that the progenitor cells arise from a specific, preexisting, cell population distinct from either hepatocytes or biliary epithelial cells.