Bacterial Folates Provide an Exogenous Signal for C. elegans Germline Stem Cell Proliferation.
Bacterial Folates Provide an Exogenous Signal for C. elegans Germline Stem Cell Proliferation.
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DOI：
10.1016/j.devcel.2016.06.013
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发表时间：
2016-07-11
影响因子：
11.8
通讯作者：
Kipreos ET
中科院分区：
文献类型：
--
作者：
Chaudhari SN;Mukherjee M;Vagasi AS;Bi G;Rahman MM;Nguyen CQ;Paul L;Selhub J;Kipreos ET
在这里，我们描述了一种线虫生殖系干细胞的体外原代培养系统。该培养系统被用来鉴定一种细菌叶酸作为生殖细胞增殖的正调控因子。叶酸是一种B-复合维生素家族，在一碳代谢中发挥作用，允许氨基酸和核苷的从头合成。我们发现叶酸10-甲酰基-四氢叶酸-谷蛋白在体外和动物体内都能刺激生殖细胞的增殖。其他可以作为维生素来治疗叶酸缺乏症的叶酸缺乏这种生殖细胞刺激活性。细菌叶酸前体二氢蝶呤在体外和体内也能促进生殖细胞的增殖，尽管它不能促进一碳代谢。叶酸受体同系物FOLR-1是10-甲酰-四氢叶酸-谷蛋白和二氢蝶呤刺激生殖细胞所必需的。这项工作将叶酸及其相关化合物定义为调节生殖细胞增殖的外源信号。Chaudhari和Mukherjee等人。描述了一种线虫生殖细胞的体外培养系统，细菌叶酸的一个亚群被鉴定为生殖细胞增殖的刺激信号。叶酸通过一种途径刺激生殖细胞的增殖，这种途径与叶酸在一碳代谢中作为维生素的作用无关。
Here we describe an in vitro primary culture system for C. elegans germline stem cells. This culture system was used to identify a bacterial folate as a positive regulator of germ cell proliferation. Folates are a family of B-complex vitamins that function in one-carbon metabolism to allow the de novo synthesis of amino acids and nucleosides. We show that germ cell proliferation is stimulated by the folate 10-formyl-tetrahydrofolate-Glun both in vitro and in animals. Other folates that can act as vitamins to rescue folate deficiency lack this germ cell stimulatory activity. The bacterial folate precursor dihydropteroate also promotes germ cell proliferation in vitro and in vivo, despite its inability to promote one-carbon metabolism. The folate receptor homolog FOLR-1 is required for the stimulation of germ cells by 10-formyl-tetrahydrofolate-Glun and dihydropteroate. This work defines a folate and folate-related compound as exogenous signals to modulate germ cell proliferation. Chaudhari and Mukherjee et al. describe an in vitro culture system for C. elegans germ cells A subset of bacterial folates was identified as a stimulatory signal for germ cell proliferation. Folates stimulate germ cell proliferation through a pathway that is independent of their role as vitamins in one-carbon metabolism.