STAT3 but not STAT1 is required for astrocyte differentiation.
STAT3 but not STAT1 is required for astrocyte differentiation.
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DOI：
10.1371/journal.pone.0086851
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Song MR
中科院分区：
文献类型：
--
作者：
Hong S;Song MR
JAK-STAT信号通路与星形胶质细胞分化有关。STAT1和STAT3都在中枢神经系统中表达，被认为对胶质细胞分化很重要，这主要是在体外证明的；然而，缺乏直接的体内证据。我们通过测试星形胶质细胞祖细胞的STAT反应性来研究STAT1和STAT3是否对星形胶质细胞发育至关重要。STAT3在神经胶质祖细胞诞生的心室区不存在，但在E16.5时开始出现在边缘区。在E18.5时，表达胶质纤维酸性蛋白（GFAP）的白质星形胶质细胞中同时存在磷酸化- stat1和磷酸化- stat3。雏鸡卵细胞电穿孔法过表达STAT3诱导脊髓星形胶质细胞祖细胞数量增加。同样，STAT3条件敲除（cKO）小鼠中STAT3的消除导致白质星形胶质细胞的消耗。有趣的是，在STAT1缺失的小鼠中，消除STAT1并不会抑制星形胶质细胞的分化，而在Stat3缺失的小鼠中，删除STAT1也不会加重胶质细胞缺陷。在各种STAT突变体存在的情况下，测量STAT结合元件和gfap启动子的活性表明，交易激活取决于STAT3的活性，而不是STAT1。未观察到STAT1和STAT3之间的协同作用。Stat1缺失的皮质祖细胞；当提供Stat3或剪接变体Stat3β时，Stat3 cKO小鼠产生星形胶质细胞，而当引入STAT1时则没有。总之，我们的研究结果表明STAT3是星形胶质细胞分化的必要和充分条件，而STAT1是可有可无的。
The JAK-STAT signaling pathway has been implicated in astrocyte differentiation. Both STAT1 and STAT3 are expressed in the central nervous system and are thought to be important for glial differentiation, as mainly demonstrated in vitro; however direct in vivo evidence is missing. We investigated whether STAT1 and STAT3 are essential for astrocyte development by testing the STAT responsiveness of astrocyte progenitors. STAT3 was absent in the ventricular zone where glial progenitors are born but begins to appear at the marginal zone at E16.5. At E18.5, both phospho-STAT1 and phospho-STAT3 were present in glial fibrillary acidic protein (GFAP)-expressing white matter astrocytes. Overexpression of STAT3 by electroporation of chicks in ovo induced increased numbers of astrocyte progenitors in the spinal cord. Likewise, elimination of STAT3 in Stat3 conditional knockout (cKO) mice resulted in depletion of white matter astrocytes. Interestingly, elimination of STAT1 in Stat1 null mice did not inhibit astrocyte differentiation and deletion of Stat1 failed to aggravate the glial defects in Stat3 cKO mice. Measuring the activity of STAT binding elements and the gfap promoter in the presence of various STAT mutants revealed that transactivation depended on the activity of STAT3 not STAT1. No synergistic interaction between STAT1 and STAT3 was observed. Cortical progenitors of Stat1 null; Stat3 cKO mice generated astrocytes when STAT3 or the splice variant Stat3β was supplied, but not when STAT1 was introduced. Together, our results suggest that STAT3 is necessary and sufficient for astrocyte differentiation whereas STAT1 is dispensable.
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DOI：
10.1016/j.bbrc.2010.03.174
发表时间：
2010-05-07
影响因子：
3.1
作者：
Kang, Kyungjun;Song, Mi-Ryoung
通讯作者：
Song, Mi-Ryoung
影响因子：
56.9
作者：
Bonni, A;Sun, Y;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4.8
作者：
Caldenhoven, E;vanDijk, TB;deGroot, RP
通讯作者：
deGroot, RP
影响因子：
4.8
作者：
Hemmann, U;Gerhartz, C;Horn, F
通讯作者：
Horn, F
影响因子：
4.8
作者：
Kang, Kyungjoon;Lee, Donghoon;Song, Mi-Ryoung
通讯作者：
Song, Mi-Ryoung