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Vitamin C alleviates aging defects in a stem cell model for Werner syndrome
  • 时间:0
  • 分类:Q813.11[生物学—生物工程] TQ466.3[化学工程—制药化工]
  • 作者机构:[1]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, [2]University of Chinese Academy of Sciences, Beijing 100049, China, [3]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China, [4]Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing 100191, China, [5]Department of Pathology,Carver College Of Medicine, University of lowa, lowa City, IA 52242, USA, [6]The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China, [7]FSU-CAS Innovation Institute, Foshan University, Foshan 528000, China, [8]Beijing Institute for Brain Disorders, Beijing 100069, China, [9]Department of Pediatrics, Beijing Shijitan Hospital Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing 100038, China
  • 相关基金:the National Basic Research Program of China (973 Program) (Nos. 2015CB964800 and 2014CB910503), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01020312), the National High Technology Research and Development Program of China (2015AA020307), the National Nat- ural Science Foundation of China (Grant Nos. 81330008, 31222039, 31201111, 81371342, 81300261, 81300677, 81271266, 81471414, 81422017, and 81401159), the Program of Beijing Municipal Science and Technology Commission (Z151100003915072), the Beijing Nat- ural Science Foundation (7141005 and 5142016), the Key Research Program of the Chinese Academy of Sciences (KJZDEW-TZ-L05), the Thousand Young Talents program of China, Youth Innovation Pro- motion Association of CAS. WZ was supported by NIH grants CA158055, CA200673, and CA203834, the V Scholar award, Breast Cancer Research Award and Oberley Award (National Cancer Insti- tute Award P30CA086862) from Holden Comprehensive Cancer Center at the University of Iowa, and startup fund from the Department of Pathology, University of lowa.
中文摘要:

沃纳症候群(WS ) 是主要影响从中层导出的纸巾的早衰混乱。我们最近用 WRN 缺乏的人的间充质的干细胞(MSC ) 开发了一个新奇人的 WS 模型。这个模型概括 WS 的许多 phenotypic 特征。基于很多化学药品的一幅屏幕,这里,我们发现维生素 C 在出现在WRN缺乏的 MSC 的早衰为许多特征施加很有效的营救包括细胞生长拘捕,增加了反应的氧种层次, telomere 摩擦,煽动性的因素的过多的分泌物,象原子薄板和 heterochromatin 的组织的破坏一样。而且,维生素 C 在一个老鼠模型在 vivo 恢复 MSC 的生存能力。定序分析的 RNA 显示维生素 C 改变涉及染色质冷凝作用,房间周期规定, DNA 复制,和 DNA 损坏的一系列基因的表示在 WRN 缺乏的 MSC 的修理小径。我们的结果为 WS MSC 作为一个恢复因素识别维生素 C,它保持作为 WS 的处理的一种新奇类型被使用的潜力。

英文摘要:

Werner syndrome (WS) is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells (MSCs). This model recapitulates many phenotypic features of WS. Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, teiomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. Moreover, Vitamin C restores in vivo viability of MSCs in a mouse model. RNA sequencing analysis indicates that Vitamin C alters the expression of a series of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways in WRN- deficient MSCs. Our results identify Vitamin C as a rejuvenating factor for WS MSCs, which holds the potential of being applied as a novel type of treatment of WS.

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