Differential requirement for utrophin in the induced pluripotent stem cell correction of muscle versus fat in muscular dystrophy mice.
Differential requirement for utrophin in the induced pluripotent stem cell correction of muscle versus fat in muscular dystrophy mice.
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DOI：
10.1371/journal.pone.0020065
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Fraidenraich D
中科院分区：
文献类型：
--
作者：
Beck AJ;Vitale JM;Zhao Q;Schneider JS;Chang C;Altaf A;Michaels J;Bhaumik M;Grange R;Fraidenraich D
杜氏肌营养不良症（DMD）是一种无法治愈的退行性肌肉疾病。我们将WT小鼠诱导的多能干细胞（iPSCs）注射到mdx和mdx∶utrophin突变胚泡中，mdx和mdx∶utrophin突变胚泡易发生DMD，且严重程度增加（mdx << mdx∶utrophin）。在mdx嵌合体中，ipsc -肌营养不良蛋白被供给肌膜，在形态和功能水平上进行纠正。肌营养不良蛋白阳性区可见肌营养不良蛋白，肌营养不良蛋白阳性区可见肌营养不良蛋白。在mdx∶utrophin突变嵌合体中，虽然iPSC-dystrophin也被供应到肌膜，但小鼠的骨骼肌组织病理学仍然很差，在肌营养不良蛋白和肌营养不良蛋白阴性区域的肌营养不良蛋白水平可以忽略。不仅仅是表达肌营养不良蛋白的组织受到iPSCs的影响。Mdx和Mdx∶utrophin小鼠的脂肪/体重比降低，但iPSC注射使Mdx和Mdx∶utrophin嵌合体的脂肪/体重比正常化，尽管Mdx∶utrophin嵌合体的脂肪中utrophin受到损害。结果表明，肌营养因子的存在是骨骼肌ipsc校正所必需的。此外，研究结果强调了ipsc -肌营养不良蛋白在与肌肉密切相关的非肌肉组织（如脂肪）的校正中潜在的（不依赖于肌营养蛋白的）非细胞自主作用。
Duchenne muscular dystrophy (DMD) is an incurable degenerative muscle disorder. We injected WT mouse induced pluripotent stem cells (iPSCs) into mdx and mdx∶utrophin mutant blastocysts, which are predisposed to develop DMD with an increasing degree of severity (mdx <<< mdx∶utrophin). In mdx chimeras, iPSC-dystrophin was supplied to the muscle sarcolemma to effect corrections at morphological and functional levels. Dystrobrevin was observed in dystrophin-positive and, at a lesser extent, utrophin-positive areas. In the mdx∶utrophin mutant chimeras, although iPSC-dystrophin was also supplied to the muscle sarcolemma, mice still displayed poor skeletal muscle histopathology, and negligible levels of dystrobrevin in dystrophin- and utrophin-negative areas. Not only dystrophin-expressing tissues are affected by iPSCs. Mdx and mdx∶utrophin mice have reduced fat/body weight ratio, but iPSC injection normalized this parameter in both mdx and mdx∶utrophin chimeras, despite the fact that utrophin was compromised in the mdx∶utrophin chimeric fat. The results suggest that the presence of utrophin is required for the iPSC-corrections in skeletal muscle. Furthermore, the results highlight a potential (utrophin-independent) non-cell autonomous role for iPSC-dystrophin in the corrections of non-muscle tissue like fat, which is intimately related to the muscle.
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影响因子：
64.5
作者：
Park IH;Arora N;Huo H;Maherali N;Ahfeldt T;Shimamura A;Lensch MW;Cowan C;Hochedlinger K;Daley GQ
通讯作者：
Daley GQ
影响因子：
12.4
作者：
Hoshiya, Hidetoshi;Kazuki, Yasuhiro;Oshimura, Mitsuo
通讯作者：
Oshimura, Mitsuo
影响因子：
3.5
作者：
Di Certo, Maria Grazia;Corbi, Nicoletta;Passananti, Claudio
通讯作者：
Passananti, Claudio
影响因子：
64.5
作者：
Grady, RM;Teng, HB;Sanes, JR
通讯作者：
Sanes, JR
影响因子：
82.9
作者：
Alter, J;Lou, F;Lu, QL
通讯作者：
Lu, QL