Early acquisition of typical metabolic features upon differentiation of mouse neural stem cells into astrocytes

Early acquisition of typical metabolic features upon differentiation of mouse neural stem cells into astrocytes
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DOI:
10.1002/glia.10348
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发表时间:
2004-04-01
期刊:
影响因子:
6.2
通讯作者:
Pellerin, L
Pellerin, L
中科院分区:
医学1区
文献类型:
--
作者:
Brunet, JF;Grollimund, L;Pellerin, L

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特定的代谢特征,如谷氨酸再摄取,与成熟星形胶质细胞的正常功能有关。在这项研究中,我们研究了这些特征是否与分化的星形胶质细胞的经典表型标志物一起获得。通过加入胎牛血清(FBS)诱导E14小鼠神经球分化为星形胶质细胞。分化程度通过逆转录-聚合酶链反应(RT-PCR)和免疫荧光GFAP和巢蛋白进行评估。神经干细胞表达巢蛋白,但不GFAP,而分化的星形胶质细胞GFAP免疫阳性,但显示低水平的巢蛋白表达。谷氨酸转运体GLAST和单羧酸转运体MCT 1的表达强烈增加伴随表型变化。此外,活跃的谷氨酸转运出现在分化的星形胶质细胞,以及他们的能力,以增加有氧糖酵解响应谷氨酸。白血病抑制因子(LIF)和睫状神经营养因子,而不是白细胞介素-6,触发星形胶质细胞的表型和形态特征的表达。此外,暴露于LIF导致通常与星形胶质细胞相关的代谢特征的出现。总之,我们的研究结果表明,收购一些特定的代谢功能的星形胶质细胞发生在其分化过程的早期,LIF代表一个候选信号,以诱导其表达。(C)2003 Wiley-Liss,Inc.
Specific metabolic features, such as glutamate reuptake, have been associated with normal functions of mature astrocytes. In this study, we examined whether these characteristics are acquired together with classical phenotypic markers of differentiated astrocytes. Differentiation of E14 mouse neurospheres into astrocytes was induced by the addition of fetal bovine serum (FBS). Degree of differentiation was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence for both GFAP and nestin. Neural stem cells expressed nestin but not GFAP, while differentiated astrocytes were immunopositive for GFAP but displayed low levels of nestin expression. A strong increase in the expression of the glutamate transporter GLAST and the monocarboxylate transporter MCT1 accompanied phenotypic changes. In addition, active glutamate transport appeared in differentiated astrocytes, as well as their capacity to increase aerobic glycolysis in response to glutamate. Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor, but not interleukin-6, triggered the expression of phenotypic and morphological characteristics of astrocytes. In addition, exposure to LIF led to the appearance of metabolic features typically associated with astrocytes. Altogether, our results show that acquisition of some specific metabolic features by astrocytes occurs early in their differentiation process and that LIF represents a candidate signal to induce their expression. (C) 2003 Wiley-Liss, Inc.