Mitochondrial metabolism directs stemness and differentiation in P19 embryonal carcinoma stem cells
Mitochondrial metabolism directs stemness and differentiation in P19 embryonal carcinoma stem cells
复制标题
DOI：
10.1038/cdd.2014.66
复制
发表时间：
2014-05
影响因子：
12.4
通讯作者：
I. Vega-Naredo;R. Loureiro;K. A. Mesquita;I. Barbosa;L. Tavares;A. Branco;J. R. Erickson;J. Holy-J
中科院分区：
文献类型：
--
作者：
I. Vega-Naredo;R. Loureiro;K. A. Mesquita;I. Barbosa;L. Tavares;A. Branco;J. R. Erickson;J. Holy-J
线粒体代谢与干细胞（SC）的细胞活力和分化之间的关系仍然知之甚少。在本研究中，我们比较了P19 SC分化前后的线粒体生理和代谢，并提出了线粒体活性，细胞分化和干性之间的关联的独特指纹。与其分化的对应物相比，P19 SC的多能性与强的糖酵解谱和降低的线粒体生物发生和复杂性相关：圆形，低极化和无活性的线粒体，具有封闭的渗透性转换孔。线粒体容量的下降增加了它们对二氯醋酸盐的抵抗力。因此，通过在含有谷氨酰胺/戊酸盐的培养基中生长P19 SC来刺激线粒体功能，降低了它们的糖酵解表型，诱导了多能潜能的丧失，损害了分化，并使P19 SC对二氯乙酸盐敏感。由于这种类型的干细胞在畸胎癌发展中的核心作用，我们的研究结果强调了线粒体代谢在干性，增殖，分化和耐药性中的重要性。此外，目前的工作表明，线粒体代谢的调节作为干细胞治疗中诱导细胞分化的工具。
The relationship between mitochondrial metabolism and cell viability and differentiation in stem cells (SCs) remains poorly understood. In the present study, we compared mitochondrial physiology and metabolism between P19SCs before/after differentiation and present a unique fingerprint of the association between mitochondrial activity, cell differentiation and stemness. In comparison with their differentiated counterparts, pluripotency of P19SCs was correlated with a strong glycolytic profile and decreased mitochondrial biogenesis and complexity: round, low-polarized and inactive mitochondria with a closed permeability transition pore. This decreased mitochondrial capacity increased their resistance against dichloroacetate. Thus, stimulation of mitochondrial function by growing P19SCs in glutamine/pyruvate-containing medium reduced their glycolytic phenotype, induced loss of pluripotent potential, compromised differentiation and became P19SCs sensitive to dichloroacetate. Because of the central role of this type of SCs in teratocarcinoma development, our findings highlight the importance of mitochondrial metabolism in stemness, proliferation, differentiation and chemoresistance. In addition, the present work suggests the regulation of mitochondrial metabolism as a tool for inducing cell differentiation in stem line therapies.