Recent studies suggest that metabolic regulation may improve differentiation of cardiomyocytes derived from induced pluripotent stem cells (iPSCs). AMP-activated protein kinase (AMPK) is a master regulator of metabolic activities. We investigated whether AMPK participates in iPSC-derived cardiomyocyte differentiation. We observed that AMPK phosphorylation at Thr172 increased at day 9 but then decreased after day 11 of differentiation to cardiomyocytes. Inhibition of AMPK with compound C significantly reduced mRNA and protein expression of cardiac troponins TNNT2 and TNNI3. Moreover, sustained AMPK activation using AICAR from days 9 to 14 of differentiation increased mRNA and protein expression of both TNNT2 and TNNI3. AICAR decreased acetylation of histone 3 at Lys9 and 56 and histone 4 at Lys16 (known target sites for nuclear-localized sirtuins [SIRT1, SIRT6]), suggesting that AMPK activation enhances sirtuin activity. Sustained AMPK activation during days 9–14 of differentiation induces sirtuin-mediated histone deacetylation and may enhance cardiomyocyte differentiation from iPSCs.

最近的研究表明，代谢调节可能会改善源自诱导多能干细胞（iPSC）的心肌细胞的分化。AMP激活的蛋白激酶（AMPK）是代谢活动的主要调节剂。我们调查了AMPK是否参与iPSC衍生的心肌细胞分化。我们观察到，Thr172处的AMPK磷酸化在分化为心肌细胞的第9天增加，但在第11天后降低。用化合物C抑制AMPK会显着降低心肌肌钙蛋白TNNT2和TNNI3的mRNA和蛋白表达。此外，从分化的第9天到第14天使用AICAR进行的AMPK持续激活会增加TNNT2和TNNI3的mRNA和蛋白质表达。AICAR降低了Lys9和56处的组蛋白3和Lys16处的组蛋白4的乙酰化程度（核定位的沉默调节蛋白的已知靶位[SIRT1，SIRT6]），表明AMPK激活增强了沉默调节蛋白的活性。在分化的第9-14天，持续的AMPK激活会诱导Sirtuin介导的组蛋白去乙酰化，并可能增强iPSC诱导的心肌细胞分化。