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。
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.