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Series GSE192482 Query DataSets for GSE192482
Status Public on Aug 08, 2023
Title Post-fast refeeding enhances intestinal stem cell mediated regeneration and tumorigenesis through mTORC1 signaling and polyamine
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary For more than a century, fasting regimens have been shown to improve health, lifespan, and tissue regeneration in diverse model organisms and humans. However, important questions remain regarding how fasting and refeeding cycles stimulate stem cell output and how this influences their role in early tumor formation. Here, we demonstrate that in the mammalian intestine, a short 24-hour fast followed by a 24-hour refeeding period (that is, post-fast refeeding) and not fasting itself elevates the stemness program and regenerative capacity of Lgr5+ intestinal stem cells (ISCs). Furthermore, loss of the tumor suppressor APC in post-fast refed ISCs significantly boosts tumor incidence in the small intestine and colon compared to those in the fasted or ad libitum fed states. Mechanistically, robust induction of insulin-PI3K-mTORC1 signaling as well as elevated intestinal polyamines level increase protein synthesis in post-fast refed ISCs to mediate these changes as inhibition of mTORC1, polyamine, or protein synthesis abrogate the regenerative or tumorigenic effects of post-fast refeeding. Thus, our data indicate that post-fast refeeding leads to a burst not only in stem cell-driven regeneration but also in tumorigenicity and that careful consideration be given to fast-refeeding cycles when planning diet-based strategies.
 
Overall design One replicate each of intestinal stem and progenitor cells isolated from mice feeding at will (al), fasted for 24 hours (f), fasted followed by refeeding at will for 24 hours (rf) and refeeding plus Rapamycin.
 
Contributor(s) Shinya I, Yilmaz O
Citation(s) 36711807
Submission date Dec 22, 2021
Last update date Aug 09, 2023
Contact name Charles Arthur Whittaker
E-mail(s) charliew@mit.edu
Organization name Koch Institute
Street address 77 Mass Ave 76-189
City Cambridge
State/province MA
ZIP/Postal code 02152
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (4)
GSM5747732 AL
GSM5747733 Fast
GSM5747734 Refeed
Relations
BioProject PRJNA791635

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Supplementary file Size Download File type/resource
GSE192482_RAW.tar 76.5 Mb (http)(custom) TAR (of TAR)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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