Teslaa Tara, Teitell Michael A
Molecular Biology Institute, University of California, Los Angeles, CA, USA.
Molecular Biology Institute, University of California, Los Angeles, CA, USA Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA Department of Bioengineering, University of California, Los Angeles, CA, USA Department of Pediatrics, University of California, Los Angeles, CA, USA California NanoSystems Institute, University of California, Los Angeles, CA, USA Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA
EMBO J. 2015 Jan 13;34(2):138-53. doi: 10.15252/embj.201490446. Epub 2014 Dec 4.
Recent studies link changes in energy metabolism with the fate of pluripotent stem cells (PSCs). Safe use of PSC derivatives in regenerative medicine requires an enhanced understanding and control of factors that optimize in vitro reprogramming and differentiation protocols. Relative shifts in metabolism from naïve through "primed" pluripotent states to lineage-directed differentiation place variable demands on mitochondrial biogenesis and function for cell types with distinct energetic and biosynthetic requirements. In this context, mitochondrial respiration, network dynamics, TCA cycle function, and turnover all have the potential to influence reprogramming and differentiation outcomes. Shifts in cellular metabolism affect enzymes that control epigenetic configuration, which impacts chromatin reorganization and gene expression changes during reprogramming and differentiation. Induced PSCs (iPSCs) may have utility for modeling metabolic diseases caused by mutations in mitochondrial DNA, for which few disease models exist. Here, we explore key features of PSC energy metabolism research in mice and man and the impact this work is starting to have on our understanding of early development, disease modeling, and potential therapeutic applications.
近期研究将能量代谢变化与多能干细胞（PSC）的命运联系起来。在再生医学中安全使用PSC衍生物需要更深入地了解和控制优化体外重编程和分化方案的因素。从原始多能状态到“预激发”多能状态，再到定向分化的代谢相对转变，对具有不同能量和生物合成需求的细胞类型的线粒体生物发生和功能提出了不同的要求。在这种情况下，线粒体呼吸、网络动态、三羧酸循环功能和周转都有可能影响重编程和分化结果。细胞代谢的转变会影响控制表观遗传构型的酶，这会影响重编程和分化过程中的染色质重组和基因表达变化。诱导多能干细胞（iPSC）可能有助于建立由线粒体DNA突变引起的代谢疾病模型，目前针对此类疾病的模型很少。在这里，我们探讨了小鼠和人类PSC能量代谢研究的关键特征，以及这项工作开始对我们理解早期发育、疾病建模和潜在治疗应用产生的影响。
