BMP-induced REST regulates the establishment and maintenance of astrocytic identity.
BMP-induced REST regulates the establishment and maintenance of astrocytic identity.
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DOI：
10.1083/jcb.200908048
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发表时间：
2010-04-05
期刊：
影响因子：
--
通讯作者：
Nakashima K
中科院分区：
文献类型：
--
作者：
Kohyama J;Sanosaka T;Tokunaga A;Takatsuka E;Tsujimura K;Okano H;Nakashima K
星形胶质细胞的分化和维持由BMP信号传导促进，其诱导REST/NRSF抑制神经元基因。一旦它们分化，细胞保留其个体特征并抑制在其他细胞谱系中特异性表达的基因，但在分化期间和/或分化后如何限制替代命运选择仍不清楚。在哺乳动物中枢神经系统中，神经元、星形胶质细胞和少突胶质细胞在整个生命过程中由常见的三能神经祖细胞（NPC）产生。骨形态发生蛋白（BMPs）是已知的诱导星形胶质细胞的细胞因子。我们在这里表明，表达的转录抑制因子，RE1沉默转录（REST）/神经元限制性沉默因子（NRSF），是上调和持续的BMP信号激活过程中的星形胶质细胞分化的NPC，并限制神经元分化。我们进一步表明，在分化的星形胶质细胞中，内源性REST/NRSF与各种神经元基因相关，其功能的破坏导致其去抑制，从而解释了异位神经元基因表达如何在星形胶质细胞性状的细胞中被阻止。总的来说，我们的研究结果表明，REST/NRSF的功能作为一个分子调节器的非神经元表型的星形胶质细胞。
Astrocyte differentiation and maintenance is promoted by BMP signaling, which induces REST/NRSF to repress neuronal genes. Once they have differentiated, cells retain their individual character and repress genes that are specifically expressed in other cell lineages, but how alternative fate choice is restricted during and/or after differentiation remains unclear. In the mammalian central nervous system, neurons, astrocytes, and oligodendrocytes are generated throughout life from common tripotent neural progenitor cells (NPCs). Bone morphogenetic proteins (BMPs) are well-known astrocyte-inducing cytokines. We show here that the expression of a transcriptional repressor, RE1 silencer of transcription (REST)/neuron-restrictive silencer factor (NRSF), is up-regulated and sustained by BMP signal activation in the course of astrocytic differentiation of NPCs, and restricts neuronal differentiation. We further show that, in differentiated astrocytes, endogenous REST/NRSF associates with various neuronal genes and that disruption of its function resulted in their derepression, thereby explaining how ectopic neuronal gene expression is prevented in cells with astrocytic traits. Collectively, our results suggest that REST/NRSF functions as a molecular regulator of the nonneuronal phenotype in astrocytes.
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DOI：
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发表时间：
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影响因子：
11.1
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DOI：
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发表时间：
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影响因子：
11.1
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