Transcript profiling and lipidomic analysis of ceramide subspecies in mouse embryonic stem cells and embryoid bodies
Transcript profiling and lipidomic analysis of ceramide subspecies in mouse embryonic stem cells and embryoid bodies
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DOI：
10.1194/jlr.m000984
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发表时间：
2010-03-01
影响因子：
6.5
通讯作者：
Merrill, Alfred H., Jr.
中科院分区：
文献类型：
--
作者：
Park, Hyejung;Haynes, Christopher A.;Merrill, Alfred H., Jr.
神经酰胺 (Cers) 在胚胎发生中很重要，但尚未使用常用模型：小鼠胚胎干细胞 (mESC) 与刺绣体 (EB) 进行 Cer 代谢的基因表达以及 Cer 数量和亚种的全面分析。通过定量 RT-PCR 测量 mRNA 水平，并通过 LC-ESI/MS/MS 测量各自代谢物的量，R1 mESC 和 EB 之间的显着差异是： EB 具有较高的 CerS1 和 CerS3 mRNA，分别合成 C18- 和 C >= 24-碳二氢神经酰胺 (DH) Cer； EB 具有较高的 CerS2（对于 C24:0- 和 C24:1-）； EB 具有较低的 CerS5 + CerS6（对于 C16-）。与这些发现一致的是，EB 的 (DH) Cer 含有较高比例的 C18-、C24- 和 C26- 以及较少的 C16- 脂肪酸，并且在单己糖基 Cers 和鞘磷脂中也观察到较长的 (DH) Cer。 EB 具有较高的脂肪酰辅酶 A 延伸酶 mRNA，这些酶可产生 C18、C24 和 C26 脂肪酰辅酶 A（Elovl3 和 Elovl6），并且 CerS 的这些共底物含量较高。因此，这些研究发现基因组和代谢组学数据之间普遍存在良好的一致性，即 mESC 向 EB 的转化伴随着鞘脂和脂酰辅酶 A 的基因表达和亚种分布的大量变化。-Park, H., C. A. Haynes, A. V. Nair, M. Kulik, S. Dalton, K. Moremen 和 A. H. Merrill, Jr.小鼠胚胎干细胞和胚状体中神经酰胺亚种的概况和脂质组学分析。 J.脂质研究。 2010。51：480-489。
Ceramides (Cers) are important in embryogenesis, but no comprehensive analysis of gene expression for Cer metabolism nor the Cer amounts and subspecies has been conducted with an often used model: mouse embryonic stem cells (mESCs) versus embroid bodies (EBs). Measuring the mRNA levels by quantitative RT-PCR and the amounts of the respective metabolites by LC-ESI/MS/MS, notable differences between R1 mESCs and EBs were: EBs have higher mRNAs for CerS1 and CerS3, which synthesize C18- and C >= 24-carbons dihydroceramides (DH) Cer, respectively; EBs have higher CerS2 (for C24:0- and C24:1-); and EBs have lower CerS5 + CerS6 ( for C16-). In agreement with these findings, EBs have (DH) Cer with higher proportions of C18-, C24- and C26- and less C16- fatty acids, and longer (DH) Cer are also seen in monohexosylCers and sphingomyelins. EBs had higher mRNAs for fatty acyl-CoA elongases that produce C18-, C24-, and C26- fatty acyl-CoAs (Elovl3 and Elovl6), and higher amounts of these cosubstrates for CerS. Thus, these studies have found generally good agreement between genomic and metabolomic data in defining that conversion of mESCs to EBs is accompanied by a large number of changes in gene expression and subspecies distributions for both sphingolipids and fatty acyl-CoAs.-Park, H., C. A. Haynes, A. V. Nair, M. Kulik, S. Dalton, K. Moremen, and A. H. Merrill, Jr. Transcript profiling and lipidomic analysis of ceramide subspecies in mouse embryonic stem cells and embryoid bodies. J. Lipid Res. 2010. 51: 480-489.