TY - JOUR T1 - Plasticity of adult hepatocytes and readjustment of cell fate: a novel dogma in liver disease JF - Gut JO - Gut SP - 954 LP - 956 DO - 10.1136/gutjnl-2019-318218 VL - 68 IS - 6 AU - Francisco Javier Cubero AU - Maria Luz Martinez-Chantar Y1 - 2019/06/01 UR - http://gut.bmj.com/content/68/6/954.abstract N2 - Acute liver failure (ALF) is a life-threatening syndrome characterised by rapid hepatocellular necrosis due to various types of insults including drugs, autoimmune disorders or viral infections, and thus represents a disease with high mortality and elevated societal costs. At present, most ALF treatment strategies are rather aimed at simply preventing complications and decelerating disease progression. Unfortunately, the only curative treatment for ALF at present is liver transplantation, an option which is limited due to financial constraints, shortage of donor livers and immunosuppression-related complications.1 Therefore, novel therapeutic avenues for patients with ALF are urgently needed.Normally, mature hepatocytes can orchestrate liver regeneration on loss of liver mass. When severe liver insult occurs, however, hepatocytes are unable to differentiate and hepatic progenitor cells (HPCs) are activated. HPCs, embryonic stem cells (ES) and induced pluripotent stem cells (iPS) have been considered a potential source for cell replacement in the injured liver since they possess hepatic differentiation capacity.2 However, their clinical applicability remains still controversial. For long, it has been widely assumed that hepatocytes do not contribute directly to the progenitor or stem cell compartment. Recently, Chen and colleagues2 reported the dedifferentiation of progenitor cells from isolated mature hepatocytes, refuting the current dogma.Yet to be explored was the identification of molecular cascades that specifically dedifferentiate mature hepatocytes and activate a ‘fetal programme’. The Hippo/Yes-associated protein (YAP)-signalling pathway plays an essential role by determining cellular fates in the mammalian liver. Hippo signalling controls the phosphorylation of the transcriptional co-activator YAP whose constitutive activation in … ER -