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

Journal article
Authors Elin Möllerström
Bertil Rydenhag
Daniel Andersson
Isabell Lebkuechner
Till B. Puschmann
Meng Chen
Ulrika Wilhelmsson
Anders Ståhlberg
Kristina Malmgren
Milos Pekny
Published in Neurochemical Research
Volume 40
Issue 2
Pages 336-352
ISSN 0364-3190
Publication year 2015
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Institute of Biomedicine, Department of Pathology
Pages 336-352
Language en
Links dx.doi.org/10.1007/s11064-014-1431-...
Keywords Astrocytoma grade IV, Oligodendroglioma grade III, Glioblastoma multiforme, Single cell gene expression profiling, FIBRILLARY ACIDIC PROTEIN, STEM-CELLS, GLIOBLASTOMA-MULTIFORME, MARKER, GLIOMAS, CANCER, HETEROGENEITY, ASTROCYTES, PROLIFERATION, MAINTENANCE, Biochemistry & Molecular Biology, Neurosciences
Subject categories Biochemistry and Molecular Biology, Neurosciences

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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