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Abstract
<p id="P3">Tissue homeostasis involves a complex balance of developmental signals
and environmental
cues that dictate stem cell function. We found that dietary lipids control enteroendocrine
cell production from Drosophila posterior midgut stem cells. Dietary cholesterol influences
new intestinal cell differentiation in an Hr96-dependent manner by altering the level
and duration of Notch signaling. Exogenous lipids modulate Delta ligand and Notch
extracellular domain stability and alter their trafficking in endosomal vesicles.
Lipid-modulated Notch signaling occurs in other nutrient-dependent tissues, suggesting
that Delta trafficking in many cells is sensitive to cellular sterol levels. These
diet-mediated alterations in young animals contribute to a metabolic program that
persists after the diet changes. A low sterol diet also slows the proliferation of
enteroendocrine tumors initiated by Notch pathway disruption. Thus, a specific dietary
nutrient can modify a key intercellular signaling pathway to shift stem cell differentiation
and cause lasting changes in tissue structure and physiology.
</p>