Elsevier

Experimental Cell Research

Volume 319, Issue 14, 15 August 2013, Pages 2230-2243
Experimental Cell Research

Research Article
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

https://doi.org/10.1016/j.yexcr.2013.06.004Get rights and content
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Highlights

  • Glioma stem cells are more heterogenous than adult human neural stem cells.

  • Glioma and adult human neural stem cells share stem- and lineage- related markers.

  • Genes dysregulated in glioma stem cells are highly expressed in pluripotent cells.

  • Wnt-signaling plays an important role in glioma stem cells.

  • A 30-gene expression signature in GSCs correlates with patient survival.

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.

Abbreviations

GSC
Glioma stem cell
ahNSC
Adult human neural stem cell
CSC
Cancer stem cell
LSC
Leukemic stem cell
HSC
hematopoetic stem cell
GBM
Glioblastoma
ESC
Embryonic stem cell
iPSC
Inducible pluripotent stem cell
MSigDB
Molecular Signature Database

Keywords

Cancer stem cell
Adult human neural stem cell
Glioblastoma
Survival
Wnt
Sfrp1

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1

Contributed equally to this work.