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| Status |
Public on Mar 20, 2023 |
| Title |
Intestinal cancer modifier RNA-Seq |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cancers predominantly arise from adult stem cells accumulating somatic driver mutations, but how genetic predisposition affects the penetrance of mutations in tumor initiation is not well understood. Here, we have analyzed gene expression in tumor-prone ApcMin/+ mice on highly variant C57BL/6J and PWD/Ph genetic backgrounds. We show that activation of beta-Catenin-driven and stem cell-specific gene expression in the presence of ApcMin or following APC loss is high in B6 mouse intestines, but remains moderate in intestines carrying PWD/Ph chromosome 5, suggesting that PWD/Ph variants restrict adenoma initiation by controlling stem cell homeostasis. Gene expression of modifier candidates and DNA methylation on chromosome 5 are predominantly cis-controlled and largely reflect the parental patterns, providing a genetic basis for inheritance of tumor susceptibility.
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| Overall design |
RNA-Seq of C57BL/6 and chromosome 5 exchange (consomic) PWD/C57BL/6 Apc(Min/+) mice.
Intestinal tissues of mice were analysed by RNA sequencing. Mice analysed differ in their status of the APC tumor suppressor locus, and are either APC(+/+) (=wildtype) or APC(min/+), that is, they carry an adenoma-inducing APCmin allele. Of the latter, normal intestinal tissue and intestinal adenoma tissue is analysed. The mice also have differences in their background genome, which is either C57BL/6 or PWD/Ph or a combination of both. Mice designated C5 carry a PWD/Ph chromosome 5, while the remaining genome is C57BL/6. Tissues are usually analysed in triplicates, as indicated. Furthermore, organoids were established from some tissues and analysed by RNA-seq, as indicated. Some organoid samples were treated with 5-aza-cytidine (AZA).
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| Contributor(s) |
Herrmann BG, Morkel M |
| Citation missing |
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| Submission date |
Apr 09, 2020 |
| Last update date |
Mar 20, 2023 |
| Contact name |
Markus Morkel |
| E-mail(s) |
markus.morkel@charite.de
|
| Organization name |
Max Planck Institute for molecular Genetics
|
| Street address |
Ihnestraße 63-73
|
| City |
Berlin |
| ZIP/Postal code |
14195 |
| Country |
Germany |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (47)
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| This SubSeries is part of SuperSeries: |
| GSE148370 |
PWD/Ph-encoded genetic variants suppress ApcMin-triggered intestinal tumor formation by modulating the cellular Wnt/beta-Catenin response |
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| Relations |
| BioProject |
PRJNA624066 |
| SRA |
SRP255867 |
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