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首页> 外文期刊>Journal of cellular biochemistry. >Synthetic sulfonyl-hydrazone-1 positively regulates cardiomyogenic microRNA expression and cardiomyocyte differentiation of induced pluripotent stem cells.
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Synthetic sulfonyl-hydrazone-1 positively regulates cardiomyogenic microRNA expression and cardiomyocyte differentiation of induced pluripotent stem cells.

机译:合成的磺酰hydr-1积极调节诱导性多能干细胞的心肌微RNA表达和心肌细胞分化。

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Induced pluripotent stem cells (iPSCs) are obtained from adult cells through overexpression of pluripotency factors. iPSCs share many features with embryonic stem cells (ESCs), circumventing ethical issues, and, noteworthy, match donor's genotype. iPSCs represent therefore a valuable tool for regenerative medicine. Cardiac differentiation of ESCs can be enhanced via microRNAs (miRNAs) and small chemical compounds, which probably act as chromatin remodelers. Cardiomyogenic potential of iPSCs is currently intensely investigated for cell therapy or in vitro drug screening and disease modeling. However, influences of small compounds on iPSC-related cardiomyogenesis have not yet been investigated in details. Here, we compared the effects of two small molecules, bis-peroxo-vanadium (bpV) and sulfonyl-hydrazone-1 (SHZ) at varying concentrations, during cardiac differentiation of murine iPSCs. SHZ (5 microM) enhanced specific marker expression and cardiomyocyte yield, without loss of cell viability. In contrast, bpV showed negligible effects on cardiac differentiation rate and appeared to induce Casp3-dependent apoptosis in differentiating iPSCs. Furthermore, SHZ-treated iPSCs were able to increase beating foci rate and upregulate early and late cardiomyogenic miRNA expression (miR-1, miR-133a, and miR-208a). Thus, our results demonstrate that small chemical compounds, such as SHZ, can constitute a novel and clinically feasible strategy to improve iPSC-derived cardiac differentiation.
机译:诱导多能干细胞(iPSC)是通过多能性因子的过表达从成年细胞获得的。 iPSC与胚胎干细胞(ESC)具有许多功能,可以规避道德问题,并且值得注意的是,可以匹配供体的基因型。因此,iPSC代表了再生医学的宝贵工具。 ESC的心脏分化可以通过microRNA(miRNA)和小的化学化合物来增强,这些化合物可能充当染色质重塑剂。目前正在对iPSCs的致心肌潜力进行深入研究,以用于细胞治疗或体外药物筛选和疾病建模。但是,尚未详细研究小化合物对iPSC相关心肌发生的影响。在这里,我们比较了两种小分子双过氧钒(bpV)和磺酰--1(SHZ)在不同浓度下在小鼠iPSC心脏分化过程中的作用。 SHZ(5 microM)增强了特异性标志物的表达和心肌细胞的产量,而不会丧失细胞活力。相反,bpV对心脏分化速率的影响可忽略不计,并且在诱导iPSC分化中似乎诱导Casp3依赖性凋亡。此外,SHZ处理的iPSC能够提高跳动灶率并上调早期和晚期心肌原性miRNA的表达(miR-1,miR-133a和miR-208a)。因此,我们的结果表明,小的化学化合物(例如SHZ)可以构成改善iPSC来源的心脏分化的新颖且临床上可行的策略。

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