Mutual antagonism between Sox10 and NFIA regulates diversification of glial lineages and glioma subtypes.
Mutual antagonism between Sox10 and NFIA regulates diversification of glial lineages and glioma subtypes.
复制标题
DOI：
10.1038/nn.3790
复制
发表时间：
2014-10
影响因子：
25
通讯作者：
Deneen, Benjamin
中科院分区：
文献类型：
--
作者：
Glasgow, Stacey M.;Zhu, Wenyi;Stolt, C. Claus;Huang, Teng-Wei;Chen, Fuyi;LoTurco, Joseph J.;Neul, Jeffrey L.;Wegner, Michael;Mohila, Carrie;Deneen, Benjamin
谱系的发展和多样化是由一组独特的转录因子的协调作用来调节的。少突胶质细胞（Oligodendrocytes，OL）和星形胶质细胞（astrocytes，AS）是中枢神经系统（central nervous system，CNS）中的胶质细胞亚系，它们的相关调节因子如何协调发育和疾病过程中的谱系分化仍是一个悬而未决的问题。Sox 10和NFIA是与OL和AS相关的胶质细胞生成的关键转录调节因子。我们发现NFIA通过直接关联和拮抗其功能来抑制Sox 10诱导OL分化。相反，我们发现Sox 10拮抗NFIA功能并抑制AS分化。使用这种发展模式作为胶质瘤的模型，我们发现，这种关系类似地调节胶质瘤亚型的产生。这些研究描述了Sox 10/NFIA之间的拮抗关系，在发展过程中调节OL和AS命运的平衡，并首次证明了控制胶质细胞亚系多样化的转录过程监督胶质瘤亚型的产生。
Lineage progression and diversification is regulated by the coordinated action of unique sets of transcription factors. Oligodendrocytes (OL) and astrocytes (AS) comprise the glial sub-lineages in the central nervous system (CNS) and how their associated regulatory factors orchestrate lineage diversification during development and disease remains an open question. Sox10 and NFIA are key transcriptional regulators of gliogenesis associated with OL and AS. We found that NFIA inhibits Sox10 induction of OL differentiation through direct association and antagonism of its function. Conversely, we found that Sox10 antagonizes NFIA function and suppresses AS differentiation. Using this developmental paradigm as a model for glioma, we found that this relationship similarly regulates the generation of glioma sub-types. These studies describe the antagonistic relationship between Sox10/NFIA that regulates the balance of OL and AS fate during development and demonstrate for the first time that the transcriptional processes governing glial sub-lineage diversification oversee the generation of glioma sub-types.
登录
查看更多内容
影响因子：
5.3
作者：
Kuhlbrodt, K;Herbarth, B;Wegner, M
通讯作者：
Wegner, M
影响因子：
10.5
作者：
Stolt, CC;Rehberg, S;Wegner, M
通讯作者：
Wegner, M
DOI：
10.1126/science.1222381
发表时间：
2012-07-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tsai HH;Li H;Fuentealba LC;Molofsky AV;Taveira-Marques R;Zhuang H;Tenney A;Murnen AT;Fancy SP;Merkle F;Kessaris N;Alvarez-Buylla A;Richardson WD;Rowitch DH
通讯作者：
Rowitch DH
影响因子：
10.5
作者：
Dai, C;Celestino, JC;Holland, EC
通讯作者：
Holland, EC
影响因子：
16.2
作者：
Kang P;Lee HK;Glasgow SM;Finley M;Donti T;Gaber ZB;Graham BH;Foster AE;Novitch BG;Gronostajski RM;Deneen B
通讯作者：
Deneen B