不同年龄mdx小鼠肌肉来源成纤维细胞诱导产生的诱导多能干细胞（iPSC）的重编程效率和质量。
Reprogramming efficiency and quality of induced Pluripotent Stem Cells (iPSCs) generated from muscle-derived fibroblasts of mdx mice at different ages.
作者信息
Wang Bo, Miyagoe-Suzuki Yuko, Yada Erica, Ito Naoki, Nishiyama Takashi, Nakamura Miho, Ono Yusuke, Motohashi Norio, Segawa Makoto, Masuda Satoru, Takeda Shin'ichi
机构信息
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan; 1.Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira 187-8502, Japan 2.Department of Biological Information, Tokyo Institute of Technology, Yokohama 226-8501, Japan and 1Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan 2Department of Life Sciences, The University of Tokyo, 3-8-1 Komaba, Tokyo 153-890, Japan.
出版信息
PLoS Curr. 2011 Oct 27;3:RRN1274. doi: 10.1371/currents.RRN1274.
Induced pluripotent stem cells (iPSCs) hold promise as a potential treatment for Duchenne muscular dystrophy (DMD). To determine the impact of the donor's age on reprogramming, we generated iPSCs from muscle-derived fibroblasts (MuFs) of mdx mice aged 6 weeks, 6 months, and 14 months. MuFs from 14-month-old mdx mice showed lower proliferative activity and lower reprogramming efficiency, compared with those from younger mdx mice. Furthermore, iPSCs derived from 14-month-old mdx mice (14m-MuF-iPSCs) gradually lost Nanog expression, and regressed in conventional ES medium during passages. Interestingly, inhibition of TGF-β signaling and BMP signaling stabilized Nanog expression and promoted self-renewal of 14m-MuF-iPSCs. Finally, rescued mdx-derived iPSCs efficiently differentiated into the skeletal muscle lineage.
诱导多能干细胞（iPSCs）有望成为杜氏肌营养不良症（DMD）的一种潜在治疗方法。为了确定供体年龄对重编程的影响，我们从6周龄、6月龄和14月龄的mdx小鼠的肌肉来源成纤维细胞（MuFs）中生成了iPSCs。与年轻mdx小鼠的MuFs相比，14月龄mdx小鼠的MuFs显示出较低的增殖活性和较低的重编程效率。此外，来自14月龄mdx小鼠的iPSCs（14m-MuF-iPSCs）逐渐失去Nanog表达，并在传代过程中在传统ES培养基中发生退化。有趣的是，抑制TGF-β信号和BMP信号可稳定Nanog表达并促进14m-MuF-iPSCs的自我更新。最后，拯救后的mdx来源的iPSCs有效地分化为骨骼肌谱系。
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