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The influence of tissue spatial geometry and functional organisation on liver regeneration

Aloia, L; (2021) The influence of tissue spatial geometry and functional organisation on liver regeneration. Seminars in Cell & Developmental Biology 10.1016/j.semcdb.2021.09.011. (In press). Green open access

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Abstract

The adult liver exerts crucial functions, including nutrient metabolism and storage, bile production and drug detoxification. These complex functions expose the liver to constant damage induced by toxins, metabolic intermediates and oxidative stress. However, the adult liver exhibits an exceptional regenerative potential, which allows fast and efficient restoration of tissue architecture and function both after tissue resection and toxic damage. To accomplish its vital role, the liver shows a peculiar tissue architecture into functional units, which follow the gradient of oxygen and nutrients within the parenchyma. Much less is known about the influence of tissue spatial geometry and functional organisation on adult liver regeneration. Here I examine the experimental evidence in mouse models showing that the spatial organisation of the epithelial and mesenchymal compartments plays a key role in liver regeneration and favours the establishment of regenerative adult liver progenitors following liver injury. I also discuss the advantages and limitations of human and mouse 3D hepatic organoid systems, which recapitulate key aspects of liver function and architecture, as models of liver regeneration and disease. Finally, I analyse the role of the YAP/TAZ transcriptional co-activators as a central hub sensing the extra-cellular matrix (ECM), metabolic and epigenetic remodelling that regulate liver regeneration and promote liver disease, such as fibrosis, chronic liver disease and liver cancer. Together, the findings summarised here demonstrate that local physical and functional cellular interactions determined by the liver peculiar spatial geometry, play a crucial role in liver regeneration, and that their alterations have important implications for human liver disease.

Type: Article
Title: The influence of tissue spatial geometry and functional organisation on liver regeneration
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.semcdb.2021.09.011
Publisher version: https://doi.org/10.1016/j.semcdb.2021.09.011
Language: English
Additional information: © 2021 Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/)
Keywords: Fibrosis, Liver progenitors, Liver regeneration, Organoids, Tissue geometry, YAP
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10136084
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