Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes.
Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes.
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DOI：
10.1016/j.celrep.2013.04.035
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发表时间：
2013-06-27
期刊：
影响因子：
8.8
通讯作者：
Goldman SA
中科院分区：
文献类型：
--
作者：
Auvergne RM;Sim FJ;Wang S;Chandler-Militello D;Burch J;Al Fanek Y;Davis D;Benraiss A;Walter K;Achanta P;Johnson M;Quinones-Hinojosa A;Natesan S;Ford HL;Goldman SA
胶质祖细胞（GPCs）是恶性胶质瘤的潜在来源。我们使用基于A2 B5的分选从跨越WHO分级II-IV的人类胶质瘤中提取致瘤性GPC。mRNA分析鉴定了一组基因，这些基因将肿瘤起始祖细胞（TPC）与从正常白色物质中分离的A2 B5 + GPC区分开来。一组核心基因和途径在A2 B5 + TPC中显著失调，包括转录因子SIX 1及其主要辅因子EYA 1和DACH 2。SIX 1的shRNAi沉默在体外和体内抑制胶质瘤TPC的扩增，表明SIX 1-EYA 1-DACH 2系统在胶质瘤发生或进展中的关键且未被认识的作用。通过比较胶质瘤TPC与正常GPC的表达模式，我们已经确定了一组离散的途径，通过这些途径可以更好地理解胶质瘤的发生，并更有针对性。
Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning WHO grades II-IV. mRNA profiling identified a cohort of genes that distinguished tumor-initiating progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, that included the transcription factor SIX1, and its principal co-factors, EYA1 and DACH2. shRNAi 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 to normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood, and more specifically targeted.