Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State?
Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State?
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DOI：
10.1089/rej.2010.1102
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发表时间：
2011-08-01
影响因子：
2.6
通讯作者：
Storch, Alexander
中科院分区：
文献类型：
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作者：
Loewenbrueck, Kai F.;Fuchs, Beate;Storch, Alexander
最近，在1.28 ppm的质子磁共振波谱（H-1-MRS）的神经干细胞（NSCs）的峰被引入作为体内神经发生的非干预性生物标志物。这将是一个迫切需要在人类的翻译研究有关成人神经发生的有益作用，大脑的结构和功能的完整性。然而，许多人担心提出的信号作为神经干细胞的特异性标记物的有效性。该峰值还与细胞类型无关的现象如凋亡或坏死有关。因此，我们比较了各种未成熟干细胞群体中的1.28 ppm峰值，包括胚胎干细胞、小鼠胚胎成纤维细胞、胚胎干细胞和诱导多能干细胞衍生的NSC、离体分离的胚胎NSC以及来自不同胚层的成熟和肿瘤细胞类型。为了将积分峰强度与细胞死亡相关联，我们用喜树碱诱导凋亡，用叠氮化钠诱导坏死。在大多数细胞类型和大多数但不是全部的NSCH培养物中发现1.28 ppm的峰，表明对NSCs没有特异性。1.28 ppm共振的强度与凋亡率显著相关，但与坏死率、细胞周期时相分布、细胞大小或类型无关。多元回归分析显示，仅凋亡的峰强度具有显著的预测值。在这种情况下，它的特异性细胞凋亡作为一个主要的选择过程中的神经发生可能表明这种共振作为一个间接的标志物在体内神经发生。
Recently, a peak at 1.28 ppm in proton magnetic resonance spectroscopy (H-1-MRS) of neural stem cells (NSCs) was introduced as a noninterventional biomarker for neurogenesis in vivo. This would be an urgently needed requisite for translational studies in humans regarding the beneficial role of adult neurogenesis for the structural and functional integrity of the brain. However, many concerns have risen about the validity of the proposed signal as a specific marker for NSCs. The peak has also been related to cell-type-independent phenomena such as apoptosis or necrosis. Thus, we compared the 1.28-ppm peak in various immature stem cell populations, including embryonic stem cells, mouse embryonic fibroblasts, embryonic stem cell-and induced pluripotent stem cell-derived NSCs, ex vivo isolated embryonic NSCs, as well as mature and tumor cell types from different germ layers. To correlate the integral peak intensity with cell death, we induced both apoptosis with camptothecin and necrosis with sodium azide. A peak at 1.28 ppm was found in most cell types, and in most, but not all, NSCH cultures, demonstrating no specificity for NSCs. The intensities of the 1.28-ppm resonance significantly correlated with the rate of apoptosis, but not with the rate of necrosis, cell cycle phase distribution, cell size, or type. Multiple regression analysis displayed a significant predictive value of the peak intensity for apoptosis only. In this context, its specificity for apoptosis as a major selection process during neurogenesis may suggest this resonance as an indirect marker for neurogenesis in vivo.