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| Status |
Public on Jul 24, 2023 |
| Title |
Myc regulates the lineage commitment of transformed hepatocytes during liver tumorigenesis (ATAC-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The two oncogenes Myc and Kras cooperate to drive tumorigenesis and tumor suppressive pathways, to regulate the tumor microenvironment and to respond to immuno-therapies in different types of cancer. However, the interactions between Myc and Kras in cancer plasticity remain largely unknown. Primary liver cancer (PLC) comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), two tumor subtypes which are morphologically and clinically different, and cell intrinsic molecular mechanisms that lead to the onset of HCC or ICC remain elusive. Here using a mouse model of KrasG12D-driven ICC we show that Myc overexpression switches the tumorigenesis towards HCC. Lineage tracing experiments showed that this switch occurred in KrasG12D transformed hepatocyte fated to develop into ICC. Since cell fate decisions during lineage differentiation are coordinately regulated by transcriptional and epigenetic changes, we took advantage of transcriptomic (RNA-seq) and chromatin accessibility (ATAC-seq) profiling to analyze hepatocytes transformed either with KrasG12D only or with KrasG12D and Myc. We identified Foxa1, Foxa2 and Ets1 as the major transcription factors responsible of the lineage commitment of transformed hepatocytes towards ICC or HCC, a function that is conserved also in humans. Altogether, our study describes an unanticipated cell intrinsic mechanism of lineage determination during the development of primary liver cancer orchestrated by the oncogene Myc.
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| Overall design |
ATAC-seq profiling of primary hepatocytes transformed with KrasG12D alone (triplicate) or in combination with Myc (triplicate). Untransformed hepatocytes (duplicate) were also profiled.
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| Contributor(s) |
D'Artista L, Barozzi I, Zender L |
| Citation(s) |
36906109 |
| |
| Submission date |
Aug 24, 2020 |
| Last update date |
Jul 25, 2023 |
| Contact name |
Iros Barozzi |
| E-mail(s) |
iros.barozzi@meduniwien.ac.at
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| Organization name |
Medical University Vienna
|
| Street address |
Borschkegasse 8a
|
| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE156746 |
Myc regulates the lineage commitment of transformed hepatocytes during liver tumorigenesis |
|
| Relations |
| BioProject |
PRJNA658961 |
| SRA |
SRP278608 |
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