This may be due to context-dependent differences between Notch1 and Notch2, different transgene expression levels, or targeting of different cellular compartments including microenvironmental interaction issues. Regarding different roles of Notch1 and Notch2, we previously established a pivotal role of Notch2, but not Notch1, during development.7 In line with these data it is also reasonable to propose Notch2 as the primary Notch mTOR inhibitor receptor mediating biliary transdifferentiation of adult hepatocytes. We did not detect any lobular biliary structures

in R26N2ICHNF1βCreERT2 livers; however, we identified Notch2 signaling as a potential regulator of the adult liver progenitor compartment, as a significant ductular reaction was observed. This attractive presumption is supported by recent data derived from rodent oval cell models by means of pharmacological Notch inhibition that suggested Notch to be important for an effective oval cell response.11, 35 In summary, not only embryonic hepatoblasts but also mature hepatocytes exhibit a marked plasticity to canonical Notch2 signaling by biliary lineage commitment XL765 and morphogenesis. The particular transcriptional target(s) of Notch2 mediating lineage commitment and morphogenesis of both embryonic and adult liver cells remain to be

identified. Nevertheless, our results support the emerging concept that liver repair mechanisms in adulthood such as ductular reactions or transdifferentiation of hepatocytes recapitulate developmental processes using signaling pathways that are normally active

during embryogenesis. However, the precise role of Notch in hepatocyte transdifferentiation and progenitor cell-mediated liver regeneration awaits to be characterized in the setting of specific liver injury models with genetic compartment-specific Notch loss-of-function and gain-of-function models. We thank Stephanie Dürl and Silvia Krutsch for excellent laboratory assistance. We thank Ryoichiro Kageyama, (Kyoto University, Japan) for providing Hes1F/F mice. Additional Supporting Information may be found in the online selleck version of this article. “
“Posthepatectomy liver failure (PHLF) is a fatal complication after partial hepatectomy. Prediction of PHLF based on preoperative liver function test and the functional liver volume to be resected is crucial. Chronic liver injury results in liver fibrosis that is directly associated with liver dysfunction. Recently liver stiffness measurement (LSM) is gaining popularity as a noninvasive assessment for liver fibrosis. In this study we aimed to evaluate the usefulness of LSM for predicting PHLF. We enrolled two hundreds and thirty-four patients (152 primary liver tumors and 81 metastatic liver tumors) undergoing partial hepatec-tomy between August 2011 and April 2014.