Marzoog Basheer Abdullah
Department of Normal and Pathological Physiology, National Research Mordovia State University, Bolshevitskaya Street, 68, Saransk, Rep. Mordovia, 430005, Russia.
Curr Mol Med. 2023;23(3):232-238. doi: 10.2174/1566524022666220216123650.
Myocardial cell injury and following sequelae are the primary reasons for death globally. Unfortunately, myocardiocytes in adults have limited regeneration capacity. Therefore, the generation of neo myocardiocytes from non-myocardial cells is a surrogate strategy. Transcription factors (TFs) can be recruited to achieve this tremendous goal. Transcriptomic analyses have suggested that GATA, Mef2c, and Tbx5 (GMT cocktail) are master TFs to transdifferentiate/reprogram cell linage of fibroblasts, somatic cells, mesodermal cells into myocardiocytes. However, adding MESP1, MYOCD, ESRRG, and ZFPM2 TFs induces the generation of more efficient and physiomorphological features for induced myocardiocytes. Moreover, the same cocktail of transcription factors can induce the proliferation and differentiation of induced/pluripotent stem cells into myocardial cells. Amelioration of impaired myocardial cells involves the activation of healing transcription factors, which are induced by inflammation mediators; IL6, tumor growth factor β, and IL22. Transcription factors regulate the cellular and subcellular physiology of myocardiocytes to include mitotic cell cycling regulation, karyokinesis and cytokinesis, hypertrophic growth, adult sarcomeric contractile protein gene expression, fatty acid metabolism, and mitochondrial biogenesis and maturation. Cell therapy by transcription factors can be applied to cardiogenesis and ameliorating impaired cardiocytes. Transcription factors are the cornerstone in cell differentiation.
心肌细胞损伤及其后续后遗症是全球范围内死亡的主要原因。不幸的是，成人心肌细胞的再生能力有限。因此，从非心肌细胞生成新的心肌细胞是一种替代策略。转录因子（TFs）可被招募来实现这一宏伟目标。转录组分析表明，GATA、Mef2c和Tbx5（GMT组合）是将成纤维细胞、体细胞、中胚层细胞的细胞谱系转分化/重编程为心肌细胞的主要转录因子。然而，添加MESP1、MYOCD、ESRRG和ZFPM2转录因子可诱导产生更高效且具有生理形态学特征的诱导心肌细胞。此外，相同的转录因子组合可诱导诱导性/多能干细胞增殖并分化为心肌细胞。改善受损心肌细胞涉及激活由炎症介质（白细胞介素6、肿瘤生长因子β和白细胞介素22）诱导的修复转录因子。转录因子调节心肌细胞的细胞和亚细胞生理学，包括有丝分裂细胞周期调控、核分裂和胞质分裂、肥大生长、成人肌节收缩蛋白基因表达、脂肪酸代谢以及线粒体生物发生和成熟。通过转录因子进行细胞治疗可应用于心脏发生和改善受损心肌细胞。转录因子是细胞分化的基石。
