Matsuoka Shinya, Armstrong Alissa R, Sampson Leesa L, Laws Kaitlin M, Drummond-Barbosa Daniela
Department of Biochemistry and Molecular Biology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland.
Department of Biochemistry and Molecular Biology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland
Genetics. 2017 Jun;206(2):953-971. doi: 10.1534/genetics.117.201921. Epub 2017 Apr 10.
Nutrients affect adult stem cells through complex mechanisms involving multiple organs. Adipocytes are highly sensitive to diet and have key metabolic roles, and obesity increases the risk for many cancers. How diet-regulated adipocyte metabolic pathways influence normal stem cell lineages, however, remains unclear. has highly conserved adipocyte metabolism and a well-characterized female germline stem cell (GSC) lineage response to diet. Here, we conducted an isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to identify diet-regulated adipocyte metabolic pathways that control the female GSC lineage. On a rich (relative to poor) diet, adipocyte Hexokinase-C and metabolic enzymes involved in pyruvate/acetyl-CoA production are upregulated, promoting a shift of glucose metabolism toward macromolecule biosynthesis. Adipocyte-specific knockdown shows that these enzymes support early GSC progeny survival. Further, enzymes catalyzing fatty acid oxidation and phosphatidylethanolamine synthesis in adipocytes promote GSC maintenance, whereas lipid and iron transport from adipocytes controls vitellogenesis and GSC number, respectively. These results show a functional relationship between specific metabolic pathways in adipocytes and distinct processes in the GSC lineage, suggesting the adipocyte metabolism-stem cell link as an important area of investigation in other stem cell systems.
营养物质通过涉及多个器官的复杂机制影响成体干细胞。脂肪细胞对饮食高度敏感并具有关键的代谢作用，肥胖会增加多种癌症的风险。然而，饮食调节的脂肪细胞代谢途径如何影响正常干细胞谱系仍不清楚。果蝇具有高度保守的脂肪细胞代谢以及对饮食有明确特征的雌性生殖系干细胞（GSC）谱系反应。在这里，我们进行了相对和绝对定量等压标记（iTRAQ）蛋白质组分析，以确定控制雌性GSC谱系的饮食调节脂肪细胞代谢途径。在丰富（相对于贫乏）饮食条件下，脂肪细胞己糖激酶-C以及参与丙酮酸/乙酰辅酶A生成的代谢酶上调，促进葡萄糖代谢向大分子生物合成的转变。脂肪细胞特异性敲低表明这些酶支持早期GSC后代的存活。此外，催化脂肪细胞中脂肪酸氧化和磷脂酰乙醇胺合成的酶促进GSC的维持，而来自脂肪细胞的脂质和铁运输分别控制卵黄发生和GSC数量。这些结果表明脂肪细胞中特定代谢途径与GSC谱系中不同过程之间存在功能关系，提示脂肪细胞代谢与干细胞的联系是其他干细胞系统中一个重要的研究领域。
