title: Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes.
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 in vitro and in vivo, 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.
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA. romane_auvergne@urmc.rochester.edu
authors.forename: Romane M
authors.initials: RM
authors.lastname: Auvergne
authors.forename: Fraser J
authors.initials: FJ
authors.lastname: Sim
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.forename: Devin
authors.initials: D
authors.lastname: Chandler-Militello
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Burch
authors.forename: Yazan
authors.initials: Y
authors.lastname: Al Fanek
authors.forename: Danielle
authors.initials: D
authors.lastname: Davis
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Benraiss
authors.forename: Kevin
authors.initials: K
authors.lastname: Walter
authors.forename: Pragathi
authors.initials: P
authors.lastname: Achanta
authors.forename: Mahlon
authors.initials: M
authors.lastname: Johnson
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quinones-Hinojosa
authors.forename: Sridaran
authors.initials: S
authors.lastname: Natesan
authors.forename: Heide L
authors.initials: HL
authors.lastname: Ford
authors.forename: Steven A
authors.initials: SA
authors.lastname: Goldman
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology* / Q000502:physiology*; D015533:Transcriptional Activation