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Hypothermia Stimulates Glioma Stem Spheres to Spontaneously Dedifferentiate Adjacent Non-stem Glioma Cells


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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This work was supported by the China Natural Science Foundation (81000963, 81370062, and 81302196), Jiangsu Province’s 333 Talent Program (BRA2011046), Jiangsu Province “six personnel peak” funded projects (2013-WSN-146/028), Jiangsu Province’s Natural Science Foundation (BK2012670), Medical Research Foundation by Jiangsu Province Health Department(YG201301 and Z201318), the Clinical Technology Development of Jiangsu University (JLY20120053), the Kunshan Social Development Foundation (KS1006, KS1009), Yancheng Medical Science Development Foundation (YK2013003, YK2013019), and the Suzhou Social Development Foundation (SYS201063). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

All authors have declared the sources of research funding for this manuscript and have no financial or other contractual agreements that might cause (or be perceived as causes of) conflicts of interest.

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Corresponding author

Correspondence to Jun Guo.

Additional information

Lei Shi, Xifeng Fei, Guan Sun and Zhimin Wang contributed equally to this work.

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Shi, L., Fei, X., Sun, G. et al. Hypothermia Stimulates Glioma Stem Spheres to Spontaneously Dedifferentiate Adjacent Non-stem Glioma Cells. Cell Mol Neurobiol 35, 217–230 (2015).

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  • Hypothermia
  • Glioma
  • Stem cells