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Classification of Subpopulations of Cells Within Human Primary Brain Tumors by Single Cell Gene Expression Profiling

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Abstract

Brain tumors are heterogeneous with respect to genetic and histological properties of cells within the tumor tissue. To study subpopulations of cells, we developed a protocol for obtaining viable single cells from freshly isolated human brain tissue for single cell gene expression profiling. We evaluated this technique for characterization of cell populations within brain tumor and tumor penumbra. Fresh tumor tissue was obtained from one astrocytoma grade IV and one oligodendroglioma grade III tumor as well as the tumor penumbra of the latter tumor. The tissue was dissociated into individual cells and the expression of 36 genes was assessed by reverse transcription quantitative PCR followed by data analysis. We show that tumor cells from both the astrocytoma grade IV and oligodendroglioma grade III tumor constituted cell subpopulations defined by their gene expression profiles. Some cells from the oligodendroglioma grade III tumor proper shared molecular characteristics with the cells from the penumbra of the same tumor suggesting that a subpopulation of cells within the oligodendroglioma grade III tumor consisted of normal brain cells. We conclude that subpopulations of tumor cells can be identified by using single cell gene expression profiling.

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Acknowledgments

We would like to thank Dr. Yolanda de Pablo for providing mouse brain tissue for development of the cell dissociation protocols. This work was supported by Swedish Medical Research Council (11548 to MP), ALF Gothenburg (11267 to MP, 11392 to BR, 137241 to AS), Söderbergs Foundations, Hjärnfonden, Amlöv’s Foundation, E. Jacobson’s Donation Fund, NanoNet COST Action (BM1002), EU FP 7 Program EduGlia (237956) to MP, EU FP 7 Program TargetBraIn (279017), AFA Research Foundation, Gothenburg Foundation for Neurological Research, FoU (Västra Götalandsregionen), the Swedish Cancer Society, and Wilhelm and Martina Lundgren foundation.

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Correspondence to Elin Möllerström, Bertil Rydenhag or Milos Pekny.

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Special Issue: In Honor of Michael Norenberg.

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Möllerström, E., Rydenhag, B., Andersson, D. et al. Classification of Subpopulations of Cells Within Human Primary Brain Tumors by Single Cell Gene Expression Profiling. Neurochem Res 40, 336–352 (2015). https://doi.org/10.1007/s11064-014-1431-y

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