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| Status |
Public on Feb 16, 2016 |
| Title |
High-fat diet enhances stemness and tumorigenicity of intestinal progenitors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem cells (ISCs) of the mammalian intestine. Like HFD, ex vivo treatment of intestinal organoid cultures with palmitic acid (PA), a constituent of the HFD, enhances the self-renewal potential of these organoid bodies. Mechanistically, HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-delta signature in intestinal stem and progenitor cells and pharmacologic activation of PPAR-delta recapitulates the effects that HFD has on these cells. Interestingly, HFD- and agonist-activated PPAR-delta signaling endows organoid-initiating capacity to non-stem cells and enforced PPAR-delta signaling permits these non-stem cells to form in vivo tumors upon loss of the tumor suppressor Apc. These findings highlight how diet-modulated PPAR-delta activation alters not only the function of intestinal stem and progenitor cells but also their capacity to initiate tumors.
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| Overall design |
mRNA profiles of intestinal stem cells (GFP-Hi) and progenitors (GFP-Low) from WT or HFD fed mice were generated by deep sequencing using HiSeq 2000.
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| Contributor(s) |
Yilmaz OH |
| Citation(s) |
26935695 |
| |
| Submission date |
Mar 26, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Omer H Yilmaz |
| Organization name |
Koch Institute for Integrated Cancer Research at MIT
|
| Department |
Biology
|
| Street address |
77 Massachusetts Avenue, 76-353D
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA279509 |
| SRA |
SRP056597 |
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