concept

intestinal stem cells

Also known as: ISC, ISCs, intestinal stem cell

Facts (21)

Sources

Dietary interventions as regulators of stem cell behavior in ... genesdev.cshlp.org Genes & Development 20 facts

claimHair follicle stem cells (HFSCs) and intestinal stem cells (ISCs) rely on glycolysis to sustain proliferation.

claimIntestinal stem cells (ISCs) that cannot oxidize glucose in the tricarboxylic acid (TCA) cycle exhibit enhanced proliferation and self-renewal.

claimIn ad libitum-fed mice, intestinal stem cells, but not progenitors, are the cell of origin for intestinal adenomas and adenocarcinomas.

referenceIntestinal stem cells reside at the base of the crypts of Lieberkühn, where they proliferate continuously to fuel the flux of differentiating intestinal epithelial populations in the contiguous villus.

claimBoth a high-fat diet and intermittent fasting lead to intestinal stem cell-autonomous activation of PPARδ signaling, which enhances self-renewal through partial activation of a Wnt signaling program and enhanced fatty acid oxidation.

claimCaloric restriction promotes mTORC1-dependent enhanced self-renewal in intestinal stem cells, primarily through changes induced by the Paneth cell niche.

claimA high-fat diet increases the number and proliferation of intestinal stem cells under conditions of normal intestinal homeostasis.

claimFasting increases PPAR-dependent fatty acid oxidation in intestinal stem cells (ISCs) to maintain stemness, according to Mihaylova et al. (2018).

claimIntestinal stem cells depend upon WNT signals from Paneth cells, which are the progeny of intestinal stem cells.

claimIntestinal stem cells (ISCs) are highly enriched for the expression of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), the rate-limiting enzyme for ketone biosynthesis, allowing them to engage in de novo ketogenesis even without a ketogenic diet.

referenceHelminth-derived metabolites, specifically succinate, stimulate resident innate immune cells called ILC2s to produce IL-13, which in turn skews intestinal stem cells (ISCs) to produce an excess of Tuft cells; these Tuft cells then secrete IL-25, which further fuels ILC2 proliferation in an inflammatory circuit (Schneider et al. 2018).

claimIn intestinal stem cells (ISCs), insulin receptor ablation prevents ISC proliferation by stabilizing adherens junctions.

referenceBlocking glucose entry into the tricarboxylic acid (TCA) cycle in intestinal stem cells (ISCs) enhances their self-renewal (Schell et al. 2017; Bensard et al. 2020).

claimA high-fat diet depletes Paneth cells in the intestine via activation of PPARδ signaling, which subsequently induces Wnt target genes in intestinal stem cells, as reported by Beyaz et al. (2016).

claimMetabolites derived from gastrointestinal helminths can skew the cell fate of intestinal stem cells (ISCs) and bias differentiation toward a specific lineage.

claimHigh-fat or cholesterol-rich diets and intermittent fasting directly alter intestinal stem cell and progenitor function.

referenceCaloric restriction increases both intestinal stem cell (ISC) and Paneth cell numbers, as reported by Yilmaz et al. in 2012.

claimGenetic inhibition of glucose oxidation enhances intestinal stem cell (ISC) self-renewal, serving as an orthogonal method to enhance ISC fatty acid oxidation, as reported by Bensard et al. (2020).

claimAlpha-ketoglutarate (αKG) accumulation acts as a prodifferentiation factor in several tissue types, including premalignant epidermal stem cells, intestinal stem cells, and pancreatic cancer cells.

claimIn a one-hit model of intestinal stem cells, a high-fat diet acts as a 'second hit' that enables tumor initiation, rather than an oncogenic mutation.

Cellular rejuvenation: molecular mechanisms and potential ... - Nature nature.com Nature Mar 14, 2023 1 fact

claimMetformin directly inhibits mTORC1 to improve stemness and alleviate senescence in stem cells, such as reversing aging-associated characteristics in intestinal stem cells.