In many organs, including the intestine and skin, cancers originate from cells of the stem or progenitor compartment. Despite its nomenclature, the cellular origin of hepatocellular carcinoma (HCC) remains elusive. In contrast to most organs, the liver lacks a defined stem cell population for organ maintenance. Previous studies suggest that both hepatocytes and facultative progenitor cells within the biliary compartment are capable of generating HCC. As HCCs with a progenitor signature carry a worse prognosis, understanding the origin of HCC is of clinical relevance. Here, we used complementary fate-tracing approaches to label the progenitor/biliary compartment and hepatocytes in murine hepatocarcinogenesis. In genotoxic and genetic models, HCCs arose exclusively from hepatocytes but never from the progenitor/biliary compartment. Cytokeratin 19–, A6- and α-fetoprotein–positive cells within tumors were hepatocyte derived. In summary, hepatocytes represent the cell of origin for HCC in mice, and a progenitor signature does not reflect progenitor origin, but dedifferentiation of hepatocyte-derived tumor cells.

In metal-enhanced fluorescence (MEF), the localized surface plasmon resonances of metallic nanostructures amplify the absorption of excitation light and assist in radiating the consequent fluorescence of nearby molecules to the far-field. This effect is at the base of various technologies that have strong impact on fields such as optics, medical diagnostics, and biotechnology. Among possible emission bands, those in the near-infrared (NIR) are particularly intriguing and widely used in proteomics and genomics due to its noninvasive character for biomolecules, living cells, and tissues, which greatly motivates the development of effective and, eventually, multifunctional NIR-MEF platforms. Here, we demonstrate NIR-MEF substrates based on Au nanocages micropatterned with a tight spatial control. The dependence of the fluorescence enhancement on the distance between the nanocage and the radiating dipoles is investigated experimentally and modeled by taking into account the local electric field enhancement an...