Induced pluripotent stem cells show metabolomic differences to embryonic stem cells in polyunsaturated phosphatidylcholines and primary metabolism.
Induced pluripotent stem cells show metabolomic differences to embryonic stem cells in polyunsaturated phosphatidylcholines and primary metabolism.
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DOI：
10.1371/journal.pone.0046770
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fiehn O
中科院分区：
文献类型：
--
作者：
Meissen JK;Yuen BT;Kind T;Riggs JW;Barupal DK;Knoepfler PS;Fiehn O
表观遗传学和基因组学分析表明，诱导多能干细胞不同于胚胎干细胞。根据细胞类型和培养条件，这种遗传改变可导致不同的代谢表型，这可能影响复制率、膜特性和细胞分化。我们在这里应用了一个全面的代谢组学策略，结合纳米电喷雾离子阱质谱（MS），气相色谱-飞行时间MS，亲水相互作用-和反相液相色谱-四极杆飞行时间MS检查诱导多能干细胞（iPSCs）的代谢组相比，亲本成纤维细胞以及参考胚胎干细胞（ESC）。利用超过250种已鉴定的代谢物和一系列结构未知的化合物，将定量和统计代谢组学数据映射到描述iPSC相对于其他细胞类型的代谢状态的代谢物网络上。总的来说，iPSC在代谢上表现出显著的转变，远离亲本成纤维细胞并朝向ESC，这表明几乎完全的代谢重编程。在碳水化合物或羟基酸代谢、戊糖磷酸途径代谢物或游离脂肪酸中未观察到多能细胞类型之间的差异。然而，iPSCs和ESC之间的显著差异在磷脂酰胆碱和磷脂酰乙醇胺脂质结构、必需和非必需氨基酸以及参与多胺生物合成的代谢物中是明显的。总之，我们的研究结果表明，在细胞重编程过程中，成纤维细胞的代谢组也被重编程为具有ESC样特征，但在iPSC中存在明显的选择独特差异。所鉴定的iPSC和ESC的代谢组学特征可能对多能性的维持和诱导的功能调节具有重要意义。
Induced pluripotent stem cells are different from embryonic stem cells as shown by epigenetic and genomics analyses. Depending on cell types and culture conditions, such genetic alterations can lead to different metabolic phenotypes which may impact replication rates, membrane properties and cell differentiation. We here applied a comprehensive metabolomics strategy incorporating nanoelectrospray ion trap mass spectrometry (MS), gas chromatography-time of flight MS, and hydrophilic interaction- and reversed phase-liquid chromatography-quadrupole time-of-flight MS to examine the metabolome of induced pluripotent stem cells (iPSCs) compared to parental fibroblasts as well as to reference embryonic stem cells (ESCs). With over 250 identified metabolites and a range of structurally unknown compounds, quantitative and statistical metabolome data were mapped onto a metabolite networks describing the metabolic state of iPSCs relative to other cell types. Overall iPSCs exhibited a striking shift metabolically away from parental fibroblasts and toward ESCs, suggestive of near complete metabolic reprogramming. Differences between pluripotent cell types were not observed in carbohydrate or hydroxyl acid metabolism, pentose phosphate pathway metabolites, or free fatty acids. However, significant differences between iPSCs and ESCs were evident in phosphatidylcholine and phosphatidylethanolamine lipid structures, essential and non-essential amino acids, and metabolites involved in polyamine biosynthesis. Together our findings demonstrate that during cellular reprogramming, the metabolome of fibroblasts is also reprogrammed to take on an ESC-like profile, but there are select unique differences apparent in iPSCs. The identified metabolomics signatures of iPSCs and ESCs may have important implications for functional regulation of maintenance and induction of pluripotency.
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影响因子：
64.5
作者：
Hanna JH;Saha K;Jaenisch R
通讯作者：
Jaenisch R
影响因子：
64.8
作者：
Metallo, Christian M.;Gameiro, Paulo A.;Bell, Eric L.;Mattaini, Katherine R.;Yang, Juanjuan;Hiller, Karsten;Jewell, Christopher M.;Johnson, Zachary R.;Irvine, Darrell J.;Guarente, Leonard;Kelleher, Joanne K.;Vander Heiden, Matthew G.;Iliopoulos, Othon;Stephanopoulos, Gregory
通讯作者：
Stephanopoulos, Gregory
影响因子：
29
作者：
Folmes CD;Nelson TJ;Martinez-Fernandez A;Arrell DK;Lindor JZ;Dzeja PP;Ikeda Y;Perez-Terzic C;Terzic A
通讯作者：
Terzic A
影响因子：
7.4
作者：
Kind, Tobias;Wohlgemuth, Gert;Lee, Do Yup;Lu, Yun;Palazoglu, Mine;Shahbaz, Sevini;Fiehn, Oliver
通讯作者：
Fiehn, Oliver
影响因子：
1.6
作者：
Juerchott, Kathrin;Guo, Ke-Tai;Selbig, Joachim
通讯作者：
Selbig, Joachim