Inhibition of the Combinatorial Signaling of Transforming Growth Factor-Beta and NOTCH Promotes Myotube Formation of Human Pluripotent Stem Cell-Derived Skeletal Muscle Progenitor Cells.
Inhibition of the Combinatorial Signaling of Transforming Growth Factor-Beta and NOTCH Promotes Myotube Formation of Human Pluripotent Stem Cell-Derived Skeletal Muscle Progenitor Cells.
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作者：
Choi IY;Lim HT;Che YH;Lee G;Kim YJ
了解调节人成肌细胞最终分化的信号通路对于成功的细胞移植和治疗肌营养不良症的药物筛选至关重要。为了改善hiPSC衍生的成肌细胞的肌管形成，我们在新建立的体外筛选平台中验证了13种小分子的集合，用于评估肌管形成。通过融合指数测量的肌管形成的分析显示，TGFβ信号传导与NOTCH信号传导的组合抑制增强了多核肌管产生的能力。TGFβ和NOTCH信号通路抑制剂的联合治疗以剂量依赖性方式改善了肌管形成。这种效应是通过抑制信号传导的组合机制来实现的。在健康人原代成肌细胞中验证了有效诱导多核肌管的小分子组合治疗。此外，其还应用于DMD患者iPSC衍生的成肌细胞以增强多核肌管的产生。
Understanding the signaling pathways that regulate the final differentiation of human myoblasts is essential for successful cell transplantation and drug screening for the treatment of muscular dystrophy. In an effort to improve myotube formation from hiPSC-derived myoblasts, we validated a collection of 13 small molecules in a newly established in vitro screening platform for the assessment of myotube formation. The analysis of myotube formation as measured by the fusion index showed that the combinational inhibition of the TGFβ signaling with NOTCH signaling enhances the ability of multi-nucleated myotube production. Combinational treatment of inhibitors for TGFβ and NOTCH signaling pathways improved myotube formation in a dose-dependent manner. This effect was achieved by inhibiting the combinatorial mechanism of signaling. The combination treatment of small molecules effective in inducing multinucleated myotubes was validated in healthy human primary myoblasts. In addition, it was also applied to DMD patient iPSC-derived myoblasts to enhance the generation of multinucleated myotubes.
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影响因子：
5.4
作者：
Fleming JW;Capel AJ;Rimington RP;Wheeler P;Leonard AN;Bishop NC;Davies OG;Lewis MP
通讯作者：
Lewis MP
影响因子：
28.1
作者：
Mukherjee-Clavin, Bipasha;Mi, Ruifa;Lee, Gabsang
通讯作者：
Lee, Gabsang
影响因子：
10.5
作者：
Liu, D;Black, BL;Derynck, R
通讯作者：
Derynck, R
影响因子：
7.7
作者：
Choi, In Young;Lim, Hotae;Lee, Gabsang
通讯作者：
Lee, Gabsang
DOI：
10.1073/pnas.47.11.1868
发表时间：
1961-01-01
影响因子：
11.1
作者：
KONIGSBERG, I
通讯作者：
KONIGSBERG, I