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Status |
Public on Dec 24, 2018 |
Title |
A C/EBPα–Wnt connection in gut homeostasis and carcinogenesis |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
We explored the connection between C/EBPα (CCAAT/enhancer binding protein α) and Wnt signaling in gut homeostasis and carcinogenesis. C/EBPα was expressed in human and murine intestinal epithelia in the transit amplifying region of the crypts and was absent in intestinal stem cells and Paneth cells with activated Wnt signaling. In human colorectal cancer and murine APCMin/+ polyps, C/EBPα was absent from nuclear β-catenin–positive tumor cells. In chemically induced intestinal carcinogenesis, C/EBPα KO in murine gut epithelia increased tumor volume. C/EBPα deletion extended the S-phase cell zone in intestinal organoids and activated typical proliferation gene expression signatures, including that of Wnt target genes. Genetic activation of β-catenin in organoids attenuated C/EBPα expression. Comparing gene expression of wild type and C/EBPα KO organoids by RNA sequencing aimed to identify C/EBPα dependent alterations in gene expression.
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Overall design |
These data suggest homeostatic and oncogenic suppressor functions of C/EBPα in the gut by restricting Wnt signaling.
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Contributor(s) |
Heuberger J, Hill U, Förster S, Zimmermann K, Malchin V, Kühl AA, Stein U, Vieth M, Birchmeier W, Leutz A |
Citation(s) |
30599048 |
Submission date |
Dec 17, 2018 |
Last update date |
Mar 19, 2019 |
Contact name |
Achim Leutz |
E-mail(s) |
aleutz@mdc-berlin.de
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Organization name |
MDC Berlin
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Department |
Cancer Research
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Lab |
Cell Differentiation and Tumorigenesis
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Street address |
Robert-Rössle-Str. 10
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City |
Berlin |
ZIP/Postal code |
13092 |
Country |
Germany |
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Platforms (1) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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Samples (6)
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Relations |
BioProject |
PRJNA510332 |
SRA |
SRP173598 |