Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells.
Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells.
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DOI：
10.1038/s41598-017-08232-2
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发表时间：
2017-08-14
影响因子：
4.6
通讯作者：
Takeda S
中科院分区：
文献类型：
--
作者：
Ito N;Kii I;Shimizu N;Tanaka H;Takeda S
卫星细胞包括骨骼肌中功能异质的干细胞群。分离未分化亚群并阐明其分子背景是鉴定诱导骨骼肌祖细胞重编程因子的必要条件。在这项研究中，我们发现使用酯酶敏感细胞染色试剂calcein-AM，细胞内酯酶活性区分了培养的高干性卫星细胞亚群。该亚群的基因表达分析显示，转录因子（Pax3、Mef2b和Pitx1或Pax7、Mef2b和Pitx1在胚胎成纤维细胞中，Pax7、Mef2b和Pitx1在成人成纤维细胞中）的特定组合将成纤维细胞重编程为骨骼肌祖细胞。当将这些重编程细胞移植到杜氏肌营养不良小鼠模型时，形成了dystrophin阳性的成熟肌纤维。这些结果强调了培养卫星细胞异质群体的新标记，潜在的治疗方法和退行性肌肉疾病的细胞来源。
Satellite cells comprise a functionally heterogeneous population of stem cells in skeletal muscle. Separation of an undifferentiated subpopulation and elucidation of its molecular background are necessary to identify the reprogramming factors to induce skeletal muscle progenitor cells. In this study, we found that intracellular esterase activity distinguishes a subpopulation of cultured satellite cells with high stemness using esterase-sensitive cell staining reagent, calcein-AM. Gene expression analysis of this subpopulation revealed that defined combinations of transcription factors (Pax3, Mef2b, and Pitx1 or Pax7, Mef2b, and Pitx1 in embryonic fibroblasts, and Pax7, Mef2b and MyoD in adult fibroblasts) reprogrammed fibroblasts into skeletal muscle progenitor cells. These reprogrammed cells formed Dystrophin-positive mature muscle fibers when transplanted into a mouse model of Duchenne muscular dystrophy. These results highlight the new marker for heterogenous population of cultured satellite cells, potential therapeutic approaches and cell sources for degenerative muscle diseases.
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影响因子：
3.7
作者：
Kurita R;Suda N;Sudo K;Miharada K;Hiroyama T;Miyoshi H;Tani K;Nakamura Y
通讯作者：
Nakamura Y
影响因子：
6
作者：
Motohashi, Norio;Uezumi, Akiyoshi;Takeda, Shin'ichi
通讯作者：
Takeda, Shin'ichi
影响因子：
0.7
作者：
Reijntjes, Susan;Stricker, Sigmar;Mankoo, Baljinder S.
通讯作者：
Mankoo, Baljinder S.
DOI：
10.1126/science.1180794
发表时间：
2010-01-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li L;Clevers H
通讯作者：
Clevers H
影响因子：
3.7
作者：
Gang, Eun Ji;Darabi, Radbod;Perlingeiro, Rita C. R.
通讯作者：
Perlingeiro, Rita C. R.