• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Oxidative Medicine and Cellular Longevity >Metabolic Reprogramming Autophagy and Reactive Oxygen Species Are Necessary for Primordial Germ Cell Reprogramming into Pluripotency
【2h】

Metabolic Reprogramming Autophagy and Reactive Oxygen Species Are Necessary for Primordial Germ Cell Reprogramming into Pluripotency

机译：代谢重编程自噬和活性氧物种是原始生殖细胞重编程为多能性的必要条件。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Cellular reprogramming is accompanied by a metabolic shift from oxidative phosphorylation (OXPHOS) toward glycolysis. Previous results from our laboratory showed that hypoxia alone is able to reprogram primordial germ cells (PGCs) into pluripotency and that this action is mediated by hypoxia-inducible factor 1 (HIF1). As HIF1 exerts a myriad of actions by upregulating several hundred genes, to ascertain whether the metabolic switch toward glycolysis is solely responsible for reprogramming, PGCs were cultured in the presence of a pyruvate kinase M2 isoform (PKM2) activator, or glycolysis was promoted by manipulating PPARγ. Conversely, OXPHOS was stimulated by inhibiting PDK1 activity in normoxic or in hypoxic conditions. Inhibition or promotion of autophagy and reactive oxygen species (ROS) production was performed to ascertain their role in cell reprogramming. Our results show that a metabolic shift toward glycolysis, autophagy, and mitochondrial inactivation and an early rise in ROS levels are necessary for PGC reprogramming. All of these processes are governed by HIF1/HIF2 balance and strict intermediate Oct4 levels. Histone acetylation plays a role in reprogramming and is observed under all reprogramming conditions. The pluripotent cells thus generated were unable to self-renew, probably due to insufficient Blimp1 downregulation and a lack of Klf4 and cMyc expression.
机译：细胞重编程伴随着从氧化磷酸化（OXPHOS）到糖酵解的代谢转变。我们实验室的先前结果表明，仅缺氧就能够将原始生殖细胞（PGC）重新编程为多能性，并且该作用是由缺氧诱导因子1（HIF1）介导的。由于HIF1通过上调数百个基因来发挥多种作用，从而确定向糖酵解的代谢转换是否仅由重编程引起，因此在丙酮酸激酶M2亚型（PKM2）激活剂的存在下培养PGC，或者通过操纵促进糖酵解PPARγ。相反，在缺氧或缺氧条件下，通过抑制PDK1活性可刺激OXPHOS。进行自噬和活性氧（ROS）产生的抑制或促进作用，以确定它们在细胞重编程中的作用。我们的结果表明，PGC重编程需要向糖酵解，自噬和线粒体失活的代谢转变以及ROS水平的早期升高。所有这些过程均受HIF1 / HIF2平衡和严格的Oct4中间水平控制。组蛋白乙酰化在重编程中起作用，并且在所有重编程条件下都可以观察到。由此产生的多能细胞无法自我更新，可能是由于Blimp1下调不足以及缺乏Klf4和cMyc表达所致。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号