[HTML][HTML] Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury

JR Schaub, Y Malato, C Gormond, H Willenbring - Cell reports, 2014 - cell.com
JR Schaub, Y Malato, C Gormond, H Willenbring
Cell reports, 2014cell.com
Hepatocytes provide most liver functions, but they can also proliferate and regenerate the
liver after injury. However, under some liver injury conditions, particularly chronic liver injury
where hepatocyte proliferation is impaired, liver stem cells (LSCs) are thought to replenish
lost hepatocytes. Conflicting results have been reported about the identity of LSCs and their
contribution to liver regeneration. To address this uncertainty, we followed candidate LSC
populations by genetic fate tracing in adult mice with chronic liver injury due to a choline …
Summary
Hepatocytes provide most liver functions, but they can also proliferate and regenerate the liver after injury. However, under some liver injury conditions, particularly chronic liver injury where hepatocyte proliferation is impaired, liver stem cells (LSCs) are thought to replenish lost hepatocytes. Conflicting results have been reported about the identity of LSCs and their contribution to liver regeneration. To address this uncertainty, we followed candidate LSC populations by genetic fate tracing in adult mice with chronic liver injury due to a choline-deficient, ethionine-supplemented diet. In contrast to previous studies, we failed to detect hepatocytes derived from biliary epithelial cells or mesenchymal liver cells beyond a negligible frequency. In fact, we failed to detect hepatocytes that were not derived from pre-existing hepatocytes. In conclusion, our findings argue against LSCs, or other nonhepatocyte cell types, providing a backup system for hepatocyte regeneration in this common mouse model of chronic liver injury.
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