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| Status |
Public on Oct 15, 2020 |
| Title |
Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell-of-origin. [Activation of stellate cells by tumor conditioned medium] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylationlow tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived KrasG12D/Trp53-/- mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylationlow/IFNsignhigh subtype potentially targetable by agents blocking intrinsic IFN-signaling.
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| Overall design |
Normal human pancreatic stellate cells were treated with conditioned medium from different primary PDAC cells for 12 hours. Cells were lysed and RNA was extracted.
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| Contributor(s) |
Espinet E, Trumpp A |
| Citation(s) |
33060108 |
| |
| Submission date |
Jul 10, 2019 |
| Last update date |
Nov 24, 2020 |
| Contact name |
Elisa Espinet |
| Organization name |
German Cancer Research Center
|
| Street address |
Im Neuenheimer Feld 280
|
| City |
Heidelberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (6)
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| GSM3937005 |
Stellate cells treated with stellate cell conditioned medium rep1 |
| GSM3937006 |
Stellate cells treated with stellate cell conditioned medium rep2 |
| GSM3937007 |
Stellate cells treated with PACO14 conditioned medium |
| GSM3937008 |
Stellate cells treated with PACO18 conditioned medium |
| GSM3937009 |
Stellate cells treated with PACO17 conditioned medium |
| GSM3937010 |
Stellate cells treated with PACO20 conditioned medium |
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| Relations |
| BioProject |
PRJNA553765 |
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