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| Status |
Public on Aug 01, 2014 |
| Title |
PR-SET7 inactivation causes hepatocyte necrosis and spontaneous development of hepatocellular carcinoma derived from ductal progenitor cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
PR-SET7-mediated histone-4 lysine-20 methylation has been implicated in mitotic condensation, DNA damage response and replication licencing. Here we show that PR-SET7 function in the liver is pivotal for maintaining genome integrity. Hepatocyte-specific deletion of PR-SET7 in mouse embryos resulted in G2 arrest followed by massive cell death and defect in liver organogenesis. Inactivation at postnatal stages caused cell duplication-dependent hepatocyte necrosis with unusual features of autophagy, termed "endonucleosis". Necrotic death was accompanied by inflammation, fibrosis and compensatory growth induction of neighboring hepatocytes and resident ductal progenitor cells. Prolonged necrotic-regenerative cycles coupled with oncogenic STAT3 activation replaced pre-existing hepatocytes with hepatocellular carcinoma derived entirely from ductal progenitor cells. Hepatocellular carcinoma in these mice displays a cancer stem cell gene signature specified by the co-expression of ductal progenitor markers and oncofetal genes.
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| Overall design |
Mice carrying hepatocyte specific inactivation of PR-SET7 were generated in order to investigate the function of PR-SET7 histone methyl transferase in liver organogenesis, hepatocyte proliferation and liver regeneration. P15 WT mice were injected intra-peritoneally (ip) with 25ml per kg DEN (diethyl nitrosamine). Mice were examined for RNA expression at 8 months old.
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| Contributor(s) |
Nikolaou K, Moulos P, Chalepakis G, Hatzis P, Oda H, Reinberg D, Talianidis I |
| Citation(s) |
25515659 |
| Submission date |
Aug 05, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Iannis Talianidis |
| E-mail(s) |
talianid@imbb.forth.gr
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| Organization name |
Foundation for Research and Technology - Hellas
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| Department |
Institute of Molecular Biology and Biotechnology
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| Street address |
100 N. Plastira Str
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| City |
Vassilika Vouton, Herakleion |
| State/province |
Crete |
| ZIP/Postal code |
70013 |
| Country |
Greece |
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| Platforms (1) |
| GPL18635 |
Ion Torrent Proton (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA214241 |
| SRA |
SRP028525 |
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