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

被引：74

作者：

Auvergne, Romane M. ^{[1
,2
]}

Sim, Fraser J. ^{[1
,2
,5
]}

Wang, Su ^{[1
,2
]}

Chandler-Militello, Devin ^{[1
,2
]}

Burch, Jaclyn ^{[1
,2
]}

Al Fanek, Yazan ^{[1
,2
]}

Davis, Danielle ^{[1
,2
]}

Benraiss, Abdellatif ^{[1
,2
]}

Walter, Kevin ^{[1
,3
]}

Achanta, Pragathi ^{[6
]}

Johnson, Mahlon ^{[4
]}

Quinones-Hinojosa, Alfredo ^{[6
]}

Natesan, Sridaran ^{[8
]}

Ford, Heide L. ^{[7
]}

Goldman, Steven A. ^{[1
,2
]}

机构：

[1] Univ Rochester, Med Ctr, Ctr Translat Neuromed, Rochester, NY 14642 USA

[2] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA

[3] Univ Rochester, Med Ctr, Dept Neurosurg, Rochester, NY 14642 USA

[4] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA

[5] SUNY Buffalo, Dept Pharmacol, Buffalo, NY 14214 USA

[6] Johns Hopkins Univ, Sch Med, Dept Neurosurg & Oncol, Baltimore, MD 21287 USA

[7] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA

[8] Sanofi Aventis Pharmaceut, Cambridge, MA 02139 USA

来源：

CELL REPORTS | 2013年 / 3卷 / 06期

关键词：

TUMOR-INITIATING CELLS; NEURAL STEM-CELLS; ADULT HUMAN BRAIN; HUMAN GLIOBLASTOMA; WHITE-MATTER; EXPRESSION; CANCER; GROWTH; IDENTIFICATION; MIGRATION;

D O I：

10.1016/j.celrep.2013.04.035

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：2127 / 2141

页数：15

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