title: Comparison of glioma stem cells to neural stem cells from the adult human brain identifies dysregulated Wnt- signaling and a fingerprint associated with clinical outcome.
abstract: Glioblastoma is the most common brain tumor. Median survival in unselected patients is <10 months. The tumor harbors stem-like cells that self-renew and propagate upon serial transplantation in mice, although the clinical relevance of these cells has not been well documented. We have performed the first genome-wide analysis that directly relates the gene expression profile of nine enriched populations of glioblastoma stem cells (GSCs) to five identically isolated and cultivated populations of stem cells from the normal adult human brain. Although the two cell types share common stem- and lineage-related markers, GSCs show a more heterogeneous gene expression. We identified a number of pathways that are dysregulated in GSCs. A subset of these pathways has previously been identified in leukemic stem cells, suggesting that cancer stem cells of different origin may have common features. Genes upregulated in GSCs were also highly expressed in embryonic and induced pluripotent stem cells. We found that canonical Wnt-signaling plays an important role in GSCs, but not in adult human neural stem cells. As well we identified a 30-gene signature highly overexpressed in GSCs. The expression of these signature genes correlates with clinical outcome and demonstrates the clinical relevance of GSCs.
authors.affiliation: Vilhelm Magnus Laboratory, Institute for Surgical Research, University of Oslo, Norway. cesandbe@medisin.uio.no
authors.forename: Cecilie Jonsgar
authors.initials: CJ
authors.lastname: Sandberg
authors.forename: Gabriel
authors.initials: G
authors.lastname: Altschuler
authors.forename: Jieun
authors.initials: J
authors.lastname: Jeong
authors.forename: Kirsten Kierulf
authors.initials: KK
authors.lastname: Strømme
authors.forename: Biljana
authors.initials: B
authors.lastname: Stangeland
authors.forename: Wayne
authors.initials: W
authors.lastname: Murrell
authors.forename: Unn-Hilde
authors.initials: UH
authors.lastname: Grasmo-Wendler
authors.forename: Ola
authors.initials: O
authors.lastname: Myklebost
authors.forename: Eirik
authors.initials: E
authors.lastname: Helseth
authors.forename: Einar Osland
authors.initials: EO
authors.lastname: Vik-Mo
authors.forename: Winston
authors.initials: W
authors.lastname: Hide
authors.forename: Iver A
authors.initials: IA
authors.lastname: Langmoen
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D053595:Embryonic Stem Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D005909:Glioblastoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D011379:Prognosis; D014158:Transcription, Genetic; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics*
keywords: Adult human neural stem cell; CSC; Cancer stem cell; ESC; Embryonic stem cell; GBM; GSC; Glioblastoma; Glioma stem cell; HSC; Inducible pluripotent stem cell; LSC; Leukemic stem cell; MSigDB; Molecular Signature Database; Sfrp1; Survival; Wnt; ahNSC; hematopoetic stem cell; iPSC