Inhibition of Methyltransferase Setd7 Allows the In Vitro Expansion of Myogenic Stem Cells with Improved Therapeutic Potential.
Inhibition of Methyltransferase Setd7 Allows the In Vitro Expansion of Myogenic Stem Cells with Improved Therapeutic Potential.
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DOI：
10.1016/j.stem.2017.12.010
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发表时间：
2018-02-01
期刊：
影响因子：
23.9
通讯作者：
Rossi FM
中科院分区：
文献类型：
--
作者：
Judson RN;Quarta M;Oudhoff MJ;Soliman H;Yi L;Chang CK;Loi G;Vander Werff R;Cait A;Hamer M;Blonigan J;Paine P;Doan LTN;Groppa E;He W;Su L;Zhang RH;Xu P;Eisner C;Low M;Barta I;Lewis CB;Zaph C;Karimi MM;Rando TA;Rossi FM
未成熟的、可移植的肌源性干细胞（MuSCs）无法在培养中显著扩增，这阻碍了修复受损或患病骨骼肌的细胞疗法的发展。为了克服这一限制，需要更深入地了解活化的、增殖的musc和分化引发的、移植不良的祖细胞之间转变的调节机制。在这里，我们发现甲基转移酶Setd7通过调节增殖的musc中β-catenin的核积累来促进这种转变。遗传或药理学抑制Setd7可促进musc体外扩增，并增加原代肌源性细胞培养的产量。移植后，用Setd7小分子抑制剂扩增的小鼠和人MuSCs都能更好地重新填充卫星细胞生态位，并且处理过的小鼠MuSCs在肌营养不良症的临床前模型中显示出增强的治疗潜力。因此，抑制Setd7可能有助于绕过肌肉疾病细胞治疗翻译中的一个关键障碍。
The development of cell therapy for repairing damaged or diseased skeletal muscle has been hindered by the inability to significantly expand immature, transplantable myogenic stem cells (MuSCs) in culture. To overcome this limitation, a deeper understanding of the mechanisms regulating the transition between activated, proliferating MuSCs and differentiation-primed, poorly engrafting progenitors is needed. Here, we show that methyltransferase Setd7 facilitates such transition by regulating the nuclear accumulation of β-catenin in proliferating MuSCs. Genetic or pharmacological inhibition of Setd7 promotes in vitro expansion of MuSCs and increases the yield of primary myogenic cell cultures. Upon transplantation, both mouse and human MuSCs expanded with a Setd7 small molecule inhibitor are better able to repopulate the satellite cell niche, and treated mouse MuSCs show enhanced therapeutic potential in preclinical models of muscular dystrophy. Thus, Setd7 inhibition may help bypass a key obstacle in the translation of cell therapy for muscle disease.
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影响因子：
5.8
作者：
Dumont, Nicolas A.;Bentzinger, C. Florian;Rudnicki, Michael A.
通讯作者：
Rudnicki, Michael A.
影响因子：
82.9
作者：
Dumont NA;Wang YX;von Maltzahn J;Pasut A;Bentzinger CF;Brun CE;Rudnicki MA
通讯作者：
Rudnicki MA
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.8
作者：
Garcia-Prat, Laura;Martinez-Vicente, Marta;Munoz-Canoves, Pura
通讯作者：
Munoz-Canoves, Pura