Although there have been numerous reports describing the isolation of liver progenitor cells from adult liver, their exact origin has not been clearly defined; and the role played by mature hepatocytes as direct contributors to the hepatic progenitor cell pool has remained largely unknown. Here we report strong evidence that mature hepatocytes in culture have the capacity to dedifferentiate into a population of adult liver progenitors without genetic or epigenetic manipulations. By using highly-purified mature hepatocytes, which were obtained from untreated, healthy rat liver and labeled with fluorescent dye PKH2, we found that hepatocytes in culture gave rise to a population of PKH2-positive liver progenitor cells. These cells, Liver Derived Progenitor Cells or LDPCS, which share phenotypic similarities with oval cells, were previously reported to be capable of forming mature hepatocytes both in culture and in animals. Studies done at various time points during the course of dedifferentiation cultures revealed that hepatocytes rapidly transformed into liver progenitors within one week through a transient oval cell-like stage. This finding was supported by lineage-tracing studies involving double-transgenic AlbuminCreXRosa26 mice expressing β-galactosidase exclusively in hepatocytes. Cultures set up with hepatocytes obtained from these mice resulted in generation of β-galactosidase-positive liver progenitor cells demonstrating that they were a direct dedifferentiation product of mature hepatocytes. Additionally, these progenitors differentiated into hepatocytes in vivo when transplanted into rats that had undergone retrorsine pretreatment and partial hepatectomy.
Conclusion
Our studies provide strong evidence for the unexpected plasticity of mature hepatocytes to dedifferentiate into progenitor cells in culture; and this may potentially have a significant impact on the treatment of liver diseases requiring liver or hepatocyte transplantation.
Abstract. We give three proofs, two intrinsic and one extrinsic, that every Dickson-Ganley unital U(σ), parametrized by a field automorphism σ, is non-classical if σ is not the identity, extending a result of Ganley's (Math Z 128:34-42, 1972); we prove that U(σ1) is isomorphic to U(σ2) if and only if σ1 = σ2 or σ1 = σ −1 2 ; and we determine the (design) automorphism group of U(σ) as the collineation subgroup of the ambient Dickson semifield plane stabilizing the unital. This contains as a special case the corresponding result of O'Nan's (J Algebra 20:495-511, 1965) on the classical unital.
Mathematics Subject Classification (2000). 51A35, 05B05, 17A35, 51A10, 51A45.
The main result of this article is an extension of the Second Main Theorem, of Halburd and Korhonen, for meromorphic functions of finite order. Their result replaces the counting function of the ramification divisor N ramf (r) in the classical Second Main Theorem by the counting function of a finite difference divisor Npair(r). In this article, the Second Main Theorem of Halburd and Korhonen is extended to the case of holomorphic maps into P n of finite order.
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