Stearoyl-CoA desaturases regulate intestinal stem and progenitor cell metabolism and function in response to nutrient abundance.

Authors

Kübra B Akkaya-Colak, Andrea R Keller, Maria H Festing, Khushboo Gupta, James Sledziona, Ayobami Adeniyi, Omar West, Patrick Stevens, Maciej Pietrzak, Sue E Knoblaugh, Helaina Walesewicz, Dominique A Baldwin, Nicholas C Denko, Judith A Simcox, James M Ntambi, Steven K Clinton, Maria M Mihaylova

Published in

Cell reports. Volume 45. Issue 8. Pages 117731. Aug 10, 2026. Epub Aug 10, 2026.

Abstract

Diet composition and nutrient availability play critical roles in intestinal stem and progenitor cell function and proliferation. Here, we show that stearoyl-CoA desaturases (SCDs) are regulated by nutrient abundance and link intracellular lipid metabolism to intestinal homeostasis. Pharmacological inhibition or genetic deletion of Scd1 and Scd2 in intestinal mouse organoids disrupted lipid desaturation, induced endoplasmic reticulum (ER) stress, and impaired stem and progenitor cell proliferation, effects largely mitigated by oleic acid supplementation. Intestine-specific deletion of Scd1 and Scd2 reduced the number of LGR5⁺ stem cells in vivo and was accompanied by metabolic rewiring and expansion of transient amplifying cells. Loss of Scd1 and Scd2 also reduced epithelial regeneration capacity following irradiation and exacerbated tissue damage and inflammation in a DSS-induced colitis model. Together, these findings reveal important SCD dependencies and metabolic adaptations in intestinal stem and progenitor cells that are necessary for epithelial regeneration and repair following injury.

PMID:
42579558
Bibliographic data and abstract were imported from PubMed on 12 Aug 2026.

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