Diet controls Drosophila follicle stem cell proliferation via Hedgehog sequestration and release.
Diet controls Drosophila follicle stem cell proliferation via Hedgehog sequestration and release.
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DOI：
10.1083/jcb.201212094
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发表时间：
2013-05-27
期刊：
影响因子：
--
通讯作者：
O'Reilly AM
中科院分区：
文献类型：
--
作者：
Hartman TR;Strochlic TI;Ji Y;Zinshteyn D;O'Reilly AM
饮食胆固醇水平通过调节Hedgehog蛋白定位控制果蝇卵巢中卵泡干细胞增殖。健康的饮食可以改善成体干细胞功能，延缓癌症、心脏病和神经退行性疾病等疾病的发生。确定营养物质决定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一步。在本文中，我们阐明了机制，饮食胆固醇控制上皮卵泡干细胞（FSC）增殖的苍蝇卵巢。在营养受限的果蝇中，跨膜蛋白Boi将Hedgehog（Hh）配体隔离在卵巢内Hh产生细胞的表面，限制FSC增殖。进食后，膳食胆固醇刺激S6激酶介导的Boi胞质结构域磷酸化，触发Hh释放和FSC增殖。这种机制能够对营养变化做出快速的组织特异性反应，使干细胞分裂和卵子产生适应足以使后代存活的环境条件。如果在其他系统中保存，这种机制可能会对干细胞功能的分子控制研究产生重要影响，其中低热量和低胆固醇饮食的好处开始显现。
Dietary cholesterol levels control follicle stem cell proliferation in the Drosophila ovary via regulation of Hedgehog protein localization. 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.
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DOI：
10.1073/pnas.0809144106
发表时间：
2009-01-27
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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影响因子：
11.8
作者：
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通讯作者：
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