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| Status |
Public on Jun 29, 2018 |
| Title |
Transcriptomic signature of hepatocellular carcinoma and intrahepatic cholangiocarcinoma derived from oncogenically transformed murine hepatocytes after stable knock-down of Tbx3 or Prdm5 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Primary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and therapy response. Yet, molecular actors and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here, we report that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumourigenesis. While a necroptosis associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes harbouring identical oncogenic drivers give rise to HCC if surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of murine HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage commitment factors, a function conserved in humans. Together, our study provides unprecedented insights into lineage commitment in liver tumourigenesis and explains molecularly why common liver damaging risk factors can either lead to HCC or ICC.
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| Overall design |
We established clonal cell lines from focal in vivo electroporation derived ICC and hydrodynamic tail-vein injection derived HCC (both driven by c-Myc and NrasG12V, pCaMIN vector). One single cell clone from each cell line was stably transfected with vectors harbouring doxycyclin inducible shRNA cassettes and a GFP reporter protein as well as a puromycin resitance gene via retroviral infection. For each cell line we used one control shRNA (shRen) and two independent shRNAs targeting Tbx3 (HCC) or Prdm5 (ICC). Each infection experiment was repeated two times.
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| Contributor(s) |
Zender L, Seehawer M, Heinzmann F, Bischof O, Roux P, Dore G, Rozenblum N |
| Citation(s) |
30209397 |
| Submission date |
Apr 03, 2018 |
| Last update date |
Sep 30, 2018 |
| Contact name |
Oliver Bischof |
| E-mail(s) |
oliver.bischof@pasteur.fr
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| Organization name |
Institut Pasteur
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| Department |
Cell Biology & Infection
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| Lab |
Nuclear Organization & Oncogenesis - Inserm U993
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| Street address |
28 rue du Docteur Roux
|
| City |
Paris Cedex 15 |
| ZIP/Postal code |
75724 |
| Country |
France |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE112617 |
Transcriptomic and epigenetic signatures of hepatocellular carcinoma and intrahepatic cholangiocarcinoma derived from oncogenically transformed murine hepatocytes |
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| Relations |
| BioProject |
PRJNA448525 |
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