Hypothermia Stimulates Glioma Stem Spheres to Spontaneously Dedifferentiate Adjacent Non-stem Glioma Cells
Hypothermia Stimulates Glioma Stem Spheres to Spontaneously Dedifferentiate Adjacent Non-stem Glioma Cells
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低温刺激神经胶质瘤干球自发去分化邻近的非干神经胶质瘤细胞
DOI：
10.1007/s10571-014-0114-1
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发表时间：
2014-09
影响因子：
4
通讯作者：
Guo Jun
中科院分区：
文献类型：
--
作者：
Shi Lei;Fei Xifeng;Sun Guan;Wang Zhimin;Wan Yi;Zeng Yanjun;Guo Jun
目前的干细胞生物学模型假设胶质瘤干细胞位于层级的顶端，并以单向方式分化为非干细胞后代。然而，我们在这里发现了一个相反的现象，即在低温条件下，胶质瘤干细胞球可以诱导邻近的非干细胞胶质瘤细胞自发地去分化为干细胞样细胞。有报道称，在低温条件下，亚低温可诱导hESC和IPSC分化为多能干细胞。然而，到目前为止，其对胶质瘤干细胞的作用尚不清楚。在本研究中，通过对非干细胞的示踪，我们发现它们可以被干细胞球吸引，最终进入干细胞球，成为体外干细胞球的一员。然而，这些诱导的CD133和Nestin标记阳性的干细胞不能形成明显的球状。为了更好地了解干细胞球体和干细胞样细胞在微环境变化背后的遗传差异，我们进行了细胞因子抗体阵列、癌症探路者PCR阵列和miRNA芯片阵列，证实了许多细胞因子、mRNAs和miRNAs参与了这种微环境的变化。在这项研究中，我们最重要的发现是我们发现了GSCs球核，已经发现它具有很强的增殖能力，并且能够100%形成一个大的GSCs球体。我们希望这些发现能够改变我们过去的观念，并对胶质瘤干细胞的进一步研究有所帮助，GSCs球核可以被定义为进一步研究的原始干细胞。
Current models of stem cell biology assume that glioma stem cells reside at the apices of hierarchies and differentiate into non-stem progeny in a unidirectional manner. However, here we found an opposite phenomenon that glioma stem spheres could induce adjacent non-stem glioma cells to spontaneously dedifferentiate into stem-like cells in low temperature condition. In low temperature condition, it has been reported that mild hypothermia could induce pluripotent stem cells in hESC and iPSC. However, till now, its effects on glioma stem cells were still unknown. In this study, tracking the non-stem cells, we found that they could be attracted by stem spheres, and finally enter the stem spheres to become a member of stem spheres in vitro. However, these induced stem-like cells positive of CD133 and Nestin markers could not form an obvious sphere. To better understand the genetic differences of the stem spheres and stem-like cells underlying the change of microenvironment, we carried out Cytokine antibody array, Cancer PathwayFinder PCR array, and miRNA chip array, which demonstrated that lots of cytokines, mRNAs, and miRNAs involved in this microenvironmental change. In this study, the most important discovery by us was that we found GSCs sphere cores, which has been found to have strong proliferative capacity, and be able to 100 % form a big GSCs sphere. We hope these findings can change our past concepts, and be help to the further research on gliomas stem cells, and GSCs sphere cores can be defined as the primitive stem cells for further research.
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DOI：
10.1073/pnas.1106704108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Vlashi, Erina;Lagadec, Chann;Pajonk, Frank
通讯作者：
Pajonk, Frank
影响因子：
4.2
作者：
Dongyong Zhang;Zhitao Jing;B. Qiu;A. Wu;Yun-jie Wang
通讯作者：
Dongyong Zhang;Zhitao Jing;B. Qiu;A. Wu;Yun-jie Wang
影响因子：
11.2
作者：
Ying Z;Li Y;Wu J;Zhu X;Yang Y;Tian H;Li W;Hu B;Cheng SY;Li M
通讯作者：
Li M
影响因子：
11.2
作者：
Sheila K. Singh;I. Clarke;Mizuhiko Terasaki;Victoria E Bonn;C. Hawkins;J. Squire;P. Dirks
通讯作者：
Sheila K. Singh;I. Clarke;Mizuhiko Terasaki;Victoria E Bonn;C. Hawkins;J. Squire;P. Dirks
影响因子：
46.9
作者：
R. Stupp;M. Hegi
通讯作者：
R. Stupp;M. Hegi