Energy metabolism in human pluripotent stem cells and their differentiated counterparts.
Energy metabolism in human pluripotent stem cells and their differentiated counterparts.
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DOI：
10.1371/journal.pone.0020914
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Schatten G
中科院分区：
文献类型：
--
作者：
Varum S;Rodrigues AS;Moura MB;Momcilovic O;Easley CA 4th;Ramalho-Santos J;Van Houten B;Schatten G
人多能干细胞具有产生成人生物体中所有细胞类型的能力，因此具有巨大的分化研究和基于细胞疗法的发展的潜力。尽管如此，由于这些细胞的不完全分化可能导致肿瘤生成，因此它们的使用可能会挑战。有趣的是，据报道，许多癌症类型显示出具有与干细胞相似的特征的代谢修饰。因此，与分化的对应物相比，了解人多能干细胞的代谢特性可能至关重要。此外，最近的数据还强调了不同人类多能细胞系的不同特征，即比较胚胎衍生的人类胚胎干细胞（HESC）并诱导从体细胞重编程的多能干细胞（IPSC）。
我们比较了hESC，IPSC及其躯体对应物的能量代谢。我们关注线粒体，我们跟踪了细胞器的定位和形态。此外，我们对与葡萄糖代谢相关的几种途径进行了基因表达分析，包括糖酵解，五磷酸五磷酸五羧酸（TCA）循环。此外，我们使用代谢外通量分析仪确定了氧消耗率（OCR），以及高性能液相色谱法（HPLC）的总细胞内ATP水平。最后，我们探索了与葡萄糖代谢调节有关的关键蛋白的表达。
我们的结果表明，尽管IPSC的代谢签名与hESC的签名并不相同，但是它们与hESC相结合而不是与躯体对应物聚集。 ATP水平，乳酸产生和OCR表明人多能细胞主要依赖于糖酵解来满足其能量需求。此外，我们的工作指出了人类多能干细胞可能用来维持高糖酵解速率的一些策略，例如高水平的己糖激酶II和非活性丙酮酸脱氢酶（PDH）。
Human pluripotent stem cells have the ability to generate all cell types present in the adult organism, therefore harboring great potential for the in vitro study of differentiation and for the development of cell-based therapies. Nonetheless their use may prove challenging as incomplete differentiation of these cells might lead to tumoregenicity. Interestingly, many cancer types have been reported to display metabolic modifications with features that might be similar to stem cells. Understanding the metabolic properties of human pluripotent stem cells when compared to their differentiated counterparts can thus be of crucial importance. Furthermore recent data has stressed distinct features of different human pluripotent cells lines, namely when comparing embryo-derived human embryonic stem cells (hESCs) and induced pluripotent stem cells (IPSCs) reprogrammed from somatic cells. We compared the energy metabolism of hESCs, IPSCs, and their somatic counterparts. Focusing on mitochondria, we tracked organelle localization and morphology. Furthermore we performed gene expression analysis of several pathways related to the glucose metabolism, including glycolysis, the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle. In addition we determined oxygen consumption rates (OCR) using a metabolic extracellular flux analyzer, as well as total intracellular ATP levels by high performance liquid chromatography (HPLC). Finally we explored the expression of key proteins involved in the regulation of glucose metabolism. Our results demonstrate that, although the metabolic signature of IPSCs is not identical to that of hESCs, nonetheless they cluster with hESCs rather than with their somatic counterparts. ATP levels, lactate production and OCR revealed that human pluripotent cells rely mostly on glycolysis to meet their energy demands. Furthermore, our work points to some of the strategies which human pluripotent stem cells may use to maintain high glycolytic rates, such as high levels of hexokinase II and inactive pyruvate dehydrogenase (PDH).
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影响因子：
46.9
作者：
Deng, Jie;Shoemaker, Robert;Xie, Bin;Gore, Athurva;LeProust, Emily M.;Antosiewicz-Bourget, Jessica;Egli, Dieter;Maherali, Nimet;Park, In-Hyun;Yu, Junying;Daley, George Q.;Eggan, Kevin;Hochedlinger, Konrad;Thomson, James;Wang, Wei;Gao, Yuan;Zhang, Kun
通讯作者：
Zhang, Kun
影响因子：
--
作者：
Cinelli, Paolo;Casanova, Elisa A.;Buerki, Kurt
通讯作者：
Buerki, Kurt
影响因子：
5.3
作者：
Kim, JW;Zeller, KI;Dang, CV
通讯作者：
Dang, CV
影响因子：
4.8
作者：
Heikkinen, S;Pietilä, M;Laakso, M
通讯作者：
Laakso, M
影响因子：
4.8
作者：
Lambert, AJ;Brand, MD
通讯作者：
Brand, MD