mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
What this study shows
Mice kept on calorie restriction (60% of normal intake) had more intestinal stem cells and Paneth cells, the cells that form the stem-cell niche (Lgr5+ stem cells 5.6% vs 4.3% of crypt cells, Paneth cells 9.8% vs 6.7%), and their crypts were nearly twice as likely to form organoids. In co-culture, Paneth cells from restricted mice, not stem cells, carried the boost. Restriction lowered S6 and S6K1 phosphorylation in crypts, and feeding or insulin switched on mTORC1 in Paneth cells but not in stem cells; forcing mTORC1 back on during restriction (Rheb induction or Tsc1 deletion) cancelled the effect, while one week of rapamycin copied it and did not add to restriction. The niche signal ran through higher Bst1 in Paneth cells, an enzyme that makes the paracrine messenger cyclic ADP ribose, and knocking down Bst1 removed the restriction effect in culture. Boundary: Mouse intestine and ex vivo organoid assays; restriction started in young adult mice, and no lifespan or human tissue was studied.
At a glance
| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: C57BL/6 mice on calorie restriction (60% of ad libitum intake, 4-28 weeks) or rapamycin; Lgr5-EGFP reporter mice; doxycycline-inducible Rheb transgene and inducible Tsc1 and Rictor deletion; intestinal crypt and sorted ISC/Paneth-cell organoid co-culture; Bst1 knockdown and cADPR) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | C57BL/6 mice on calorie restriction (60% of ad libitum intake, 4-28 weeks) or rapamycin; Lgr5-EGFP reporter mice; doxycycline-inducible Rheb transgene and inducible Tsc1 and Rictor deletion; intestinal crypt and sorted ISC/Paneth-cell organoid co-culture; Bst1 knockdown and cADPR |
| Journal | Nature |
| Year | 2012 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1038/nature11163 · PMID 22722868 · Free full text (PMC3387287) |
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | Calorie restriction (60% of ad libitum); rapamycin; inducible Rheb overexpression; Tsc1 or Rictor deletion; Bst1 knockdown |
| Target | mTORC1 in Paneth cells |
| Model | Mouse |
| Effect | Lower Paneth-cell mTORC1 (by CR or rapamycin) increases intestinal stem-cell number and function via Bst1/cADPR; forced mTORC1 activity blocks it |
In the Atlas
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