Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes

Romane M. Auvergne, Fraser J. Sim, Su Wang, Devin Chandler-Militello, Jaclyn Burch, Yazan AlFanek, Danielle Davis, Abdellatif Benraiss, Kevin Walter, Pragathi Achanta, Mahlon Johnson, Alfredo Quinones-Hinojosa, Sridaran Natesan, Heide L. Ford, Steven A. Goldman

Research output: Contribution to journalArticlepeer-review

Abstract

Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5+ glioma tumor progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs invitro and invivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted.

Original languageEnglish (US)
Pages (from-to)2127-2141
Number of pages15
JournalCell Reports
Volume3
Issue number6
DOIs
StatePublished - Mar 27 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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