Abstract
Adult liver cells have been considered restricted regarding their fate and lineage potential. That is, hepatocytes have been thought able only to generate hepatocytes and duct cells, only duct cells. While this may be the case for the majority of scenarios in a state of quiescence or homeostasis, evidence suggests that liver cells are capable of interconverting between cellular states of distinct phenotypic traits. This interconversion or plasticity had been suggested by classical studies using cellular markers, but recently lineage tracing approaches have proven that cells are highly plastic and retain an extraordinary ability to respond differently to normal tissue homeostasis, to tissue repair, or when challenged to expand ex vivo or to differentiate upon transplantation. Stemness, as “self‐renewal and multipotency,” seems not to be limited to a particular cell type but rather to a cellular state in which cells exhibit a high degree of plasticity and can move back and forth in different phenotypic states. For instance, upon damage cells can dedifferentiate to acquire stem cell potential that allows them to self‐renew, repopulate a damaged tissue, and then undergo differentiation. In this review, we will discuss the evidence on cellular plasticity in the liver, focusing our attention on two markers, epithelial cell adhesion molecule and leucine‐rich repeat‐containing G protein‐coupled receptor 5, which identify cells with stem cell potential. (Hepatology 2016;64:652‐662)
Highlights
The stem cell state is defined by the ability of cells to fulfill the two following criteria: self-renewal and multipotency.[1]
Cellular plasticity is understood as the propensity of a cell to, under certain circumstances, acquire the biological properties of other cells.[2]. Because stem cell potential can be defined as the ability of cells to acquire a stem cell state, stem cell potential would be a specific manifestation of plasticity.[2]. On the other hand, one could consider that this return to a more primitive state is a form of in vivo reprogramming
In zebrafish, genetic ablation of the hepatocyte compartment followed by lineage tracing resulted in ductal cells dedifferentiating and acquiring a stem cell fate, where biliary tree stem/progenitors repair the damaged liver.[27] upon complete senescence of the hepatocyte compartment, Lu and colleagues observed a similar widespread ductular reaction in the mouse.[28] recent studies indicate that following transplantation and injury, mouse hepatocytes can acquire a ductal phenotype and stem cell state and can differentiate toward hepatocytes and ductal cells upon demand.[29] in human liver failure, ductal cells are detected close to clusters of hepatocytes that express ductal markers.[30]. Whether in humans the ductal cells derive from hepatocytes or the inverse is true might be difficult to determine without the possibility of tracking the cells in vivo. These studies suggest that the adult liver cellular state is not fixed but can be modulated upon request
Summary
Adult liver cells have been considered restricted regarding their fate and lineage potential. In zebrafish, genetic ablation of the hepatocyte compartment followed by lineage tracing resulted in ductal cells dedifferentiating and acquiring a stem cell fate, where biliary tree stem/progenitors repair the damaged liver.[27] upon complete senescence of the hepatocyte compartment, Lu and colleagues observed a similar widespread ductular reaction in the mouse.[28] recent studies indicate that following transplantation and injury, mouse hepatocytes can acquire a ductal phenotype and stem cell state and can differentiate toward hepatocytes and ductal cells upon demand.[29] in human liver failure, ductal cells are detected close to clusters of hepatocytes that express ductal markers.[30] Whether in humans the ductal cells derive from hepatocytes or the inverse is true might be difficult to determine without the possibility of tracking the cells in vivo Overall, these studies suggest that the adult liver cellular state (either hepatocyte or duct) is not fixed but can be modulated upon request. Taking into account that cellular plasticity will enable cells that a priori do not exhibit stem cell properties to acquire stem cell potential if needed (self-renew and differentiate), we propose a more reconciled concept, whereby liver cells possess an extreme plasticity that allows the acquisition of different states (differentiation-stemness) depending on the environment and tissue demand (Fig. 1A)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
