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 spontaneousl...

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Veröffentlicht in:Cellular and molecular neurobiology 2015-03, Vol.35 (2), p.217-230
Hauptverfasser: Shi, Lei, Fei, Xifeng, Sun, Guan, Wang, Zhimin, Wan, Yi, Zeng, Yanjun, Guo, Jun
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container_issue 2
container_start_page 217
container_title Cellular and molecular neurobiology
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creator Shi, Lei
Fei, Xifeng
Sun, Guan
Wang, Zhimin
Wan, Yi
Zeng, Yanjun
Guo, Jun
description 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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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. 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subjects Biomedical and Life Sciences
Biomedicine
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Cell Biology
Cell Dedifferentiation
Cell Line, Tumor
Cell Proliferation
Cell Separation
Cell Tracking
Cold Temperature
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glioma - genetics
Glioma - pathology
Humans
Hypothermia, Induced
MicroRNAs - genetics
MicroRNAs - metabolism
Neoplasm Invasiveness
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Neurobiology
Neurosciences
Original Research
Spheroids, Cellular - metabolism
Spheroids, Cellular - pathology
title Hypothermia Stimulates Glioma Stem Spheres to Spontaneously Dedifferentiate Adjacent Non-stem Glioma Cells
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