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| Status |
Public on Dec 19, 2017 |
| Title |
Epigenetic memory of obesity predisposes to colorectal cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Colorectal cancer (CRC) is the third most common cancer worldwide. Obesity is a major risk factor with long-lasting effects on the predisposition to CRC even after weight loss; however, the mechanistic underpinnings remain poorly understood. Using a diet-induced obesity mouse model, we profiled cell-intrinsic alterations in colonic epithelium from young and aged obese mice compared with their age-matched controls, to gain insights into the progression of obesity-associated dysregulations in colonic cellular states. Cellular metabolic reprogramming occurred at early stage, boosting the number and function of stem/stem-like cells; while cell-intrinsic rewiring of signal transduction networks happened at later stage, promoting growth factor-independent proliferation. Strikingly, colonic DNA methylome was pre-programmed by obesity at young age priming for a tumor-prone gene signature after aging. Furthermore, obesity-related changes were substantially preserved after weight loss, potentially contributing to long-term predisposition to CRC. These findings broadened our perspectives on how obesity shapes the predisposition to CRC.
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| Overall design |
Ribo-zero RNA-Seq was performed in colonic epithelium from mice on three different dietary regimens as follows: 1) low-fat diet for 43 weeks; 2) high-fat diet for 43 weeks; 3) high-fat diet for an initial 15 weeks then switched to low-fat diet for another 28 weeks.
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| Contributor(s) |
Li R, Wade PA, Grimm SA |
| Citation(s) |
29346762 |
| |
| Submission date |
Jun 20, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Paul A Wade |
| E-mail(s) |
wadep2@niehs.nih.gov
|
| Phone |
919-541-3392
|
| Organization name |
NIEHS
|
| Department |
Laboratory of Molecular Carcinogenesis
|
| Street address |
111 TW Alexander Drive
|
| City |
Research Triangle Park |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (23)
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| Relations |
| BioProject |
PRJNA391197 |
| SRA |
SRP109869 |
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