This has been attributed to activation and differentiation of putative hepatic
progenitor cells (HPC) residing in the canals of Hering and/or metaplasia of preexisting mature epithelial cells. A novel analytic approach consisting of multiplex labeling, high-resolution whole-slide imaging (WSI), and automated image analysis was used to determine if more complex epithelial cell phenotypes preexist in normal adult human livers, which might provide an alternative explanation for disease-induced epithelial diversity. “Virtually digested” WSI enabled quantitative cytometric analyses of individual cells displayed in a variety of formats (e.g., scatterplots) while still tethered to the WSI and tissue structure. We employed biomarkers specifically associated with mature epithelial selleck screening library forms (HNF4α for hepatocytes, CK19
and HNF1β for BEC) and explored for the presence of cells with hybrid biomarker phenotypes. The results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bipotential cells likely serve as a reservoir for the epithelial diversity of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and fluid transition of BEC GDC-0068 molecular weight Protein kinase N1 to hepatocytes, and vice versa. Conclusion: Novel imaging and computational
tools enable increased information extraction from tissue samples and quantify the considerable preexistent hybrid epithelial diversity in normal human liver. This computationally enabled tissue analysis approach offers much broader potential beyond the results presented here. (HEPATOLOGY 2013) In normal human livers, routine conventional histology divides epithelial cells into hepatocytes and biliary epithelial cells (BECs). A wide variety of hepatocyte-BEC transitional phenotypes, however, quickly appear in diseased livers. Cells with transitional phenotypes are thought to arise from proliferation and differentiation of hepatic progenitor cells (HPCs)1, 2 and/or from metaplasia of mature hepatocytes and BEC.3 Otherwise, typical hepatocytes can be found in portal tract bile ducts with no connection to lobular-based hepatocytes4 and the liver responds “intelligently” to various insults by rapidly producing more BEC and/or hepatocytes, as needed.5, 6 Understanding the complexity of these wound repair responses using traditional light and electron microscopy limits the type of data that can be extracted from tissue samples.
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