Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
J Cell Biol. 2013 May 27;201(5):741-57. doi: 10.1083/jcb.201212094. Epub 2013 May 20.
A healthy diet improves adult stem cell function and delays diseases such as cancer, heart disease, and neurodegeneration. Defining molecular mechanisms by which nutrients dictate stem cell behavior is a key step toward understanding the role of diet in tissue homeostasis. In this paper, we elucidate the mechanism by which dietary cholesterol controls epithelial follicle stem cell (FSC) proliferation in the fly ovary. In nutrient-restricted flies, the transmembrane protein Boi sequesters Hedgehog (Hh) ligand at the surface of Hh-producing cells within the ovary, limiting FSC proliferation. Upon feeding, dietary cholesterol stimulates S6 kinase-mediated phosphorylation of the Boi cytoplasmic domain, triggering Hh release and FSC proliferation. This mechanism enables a rapid, tissue-specific response to nutritional changes, tailoring stem cell divisions and egg production to environmental conditions sufficient for progeny survival. If conserved in other systems, this mechanism will likely have important implications for studies on molecular control of stem cell function, in which the benefits of low calorie and low cholesterol diets are beginning to emerge.
健康饮食可改善成体干细胞功能，并延缓癌症、心脏病和神经退行性疾病等多种疾病的发生。明确营养素调控干细胞行为的分子机制是理解饮食在组织稳态中作用的关键步骤。本文中，我们阐述了膳食胆固醇调控果蝇卵巢上皮滤泡干细胞（FSC）增殖的机制。在营养受限的果蝇中，跨膜蛋白 Boi 将 Hedgehog（Hh）配体隔离在卵巢中产生 Hh 的细胞表面，从而限制 FSC 增殖。进食后，膳食胆固醇刺激 S6 激酶介导的 Boi 细胞质结构域磷酸化，触发 Hh 释放和 FSC 增殖。该机制使机体能够对营养变化做出快速的、组织特异性的反应，将干细胞分裂和卵子产生调整到足以使后代存活的环境条件。如果该机制在其他系统中保守，那么它对于研究干细胞功能的分子调控将具有重要意义，因为低热量和低胆固醇饮食的益处开始显现。
