Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
Heterogeneous filament network formation by myosin light chain isoforms effects on contractile energy output of single cardiomyocytes derived from human induced pluripotent stem cells
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DOI：
10.1016/j.reth.2016.02.009
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发表时间：
2016-03-01
影响因子：
4.3
通讯作者：
Kawabata, Kazushige
中科院分区：
文献类型：
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作者：
Mizutani, Takeomi;Furusawa, Kazuya;Kawabata, Kazushige
来源于人诱导多能干细胞（hiPSC-CM）的心肌细胞预期在心脏治疗中发挥重要作用，其中hiPSC-CM应产生足够的收缩力以泵送血液。然而，最近的研究表明，由hiPSC-CM组成的心肌模拟物的收缩性低于成人心肌。为了检查hiPSC-CM的收缩力输出减弱的机制，我们测量了单个hiPSC-CM的收缩力，并观察了心脏（有助于搏动）和非心脏（不有助于搏动）同种型的肌球蛋白II调节轻链（MRLC）的纤维分布。将单个hiPSC-CM在细胞外基质凝胶上培养，并测量施加在凝胶上的收缩力和应变能。应变能是不均匀的细胞之间，范围从0.2至5.8 pJ。MRLC亚型的收缩力测量和免疫荧光显微镜的组合显示，具有较高应变能的细胞表达的非心脏肌球蛋白II纤维相比，那些具有较低应变能的细胞。对心脏和非心脏MRLC的观察表明，MRLC异构体形成异质性细丝网络。这些结果表明，来自单个hiPSC-CM的应变能输出依赖于心脏和非心脏肌球蛋白纤维，其防止细胞体变形。(c)2016年，日本再生医学会。制作和主办：Elsevier B. V.
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are expected to play an important role in heart therapies, in which hiPSC-CMs should generate sufficient contractile force to pump blood. However, recent studies have shown that the contractility of myocardial mimics composed of hiPSC-CMs is lower than that of adult human myocardium. To examine the mechanism by which contractile force output of hiPSC-CMs is weakened, we measured the contractile force of single hiPSC-CMs and observed the fibrous distribution of myosin II regulatory light chain (MRLC) of cardiac (contributes to beating) and non-cardiac (does not contribute to beating) isoforms. Single hiPSC-CMs were cultured on an extracellular matrix gel, and the contractile force and strain energy exerted on the gel were measured. Strain energy was not uniform between cells and ranged from 0.2 to 5.8 pJ. The combination of contractile force measurement and immunofluorescent microscopy for MRLC isoforms showed that cells with higher strain energy expressed the weakened non-cardiac myosin II fibers compared to those of cells with lower strain energy. Observation of cardiac and non-cardiac MRLC showed that the MRLC isoforms formed heterogeneous filament networks. These results suggest that strain energy output from single hiPSC-CMs depends both cardiac and non-cardiac myosin fibers, which prevent deformation of the cell body. (c) 2016, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.