Relative Levels of Gli1 and Gli2 Determine the Response of Ventral Neural Stem Cells to Demyelination.
Relative Levels of Gli1 and Gli2 Determine the Response of Ventral Neural Stem Cells to Demyelination.
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DOI：
10.1016/j.stemcr.2020.10.003
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发表时间：
2020-11-10
影响因子：
5.9
通讯作者：
Samanta J
中科院分区：
文献类型：
--
作者：
Radecki DZ;Messling HM;Haggerty-Skeans JR;Bhamidipati SK;Clawson ED;Overman CA;Thatcher MM;Salzer JL;Samanta J
在许多以脱髓鞘为特征的神经系统疾病中，增强髓鞘的修复是重要的治疗目标。在健康成人大脑中，脑室下区的腹侧神经干细胞（vNSCs）（以GLI1表达为标志）不产生少突胶质细胞。然而，响应脱髓鞘，它们的后代被招募到病变处，在那里它们分化成少突胶质细胞，并且GLI 1的消融进一步增强髓鞘再生。GLI1和GLI2是密切相关的转录激活因子，但GLI2在vNSCs髓鞘再生中的作用尚不清楚。在这里，我们表明，在vNSCs的Gli1基因消融增加GLI2的表达和两个转录因子的组合损失减少了他们的后代在脱髓鞘病变的招聘和分化。这些结果表明，GLI1和GLI2在vNSCs中具有不同的、非冗余的功能，并且它们的相对水平在对脱髓鞘的响应中起着至关重要的作用。Gli1和Gli2的缺失抑制了神经干细胞后代向病变的募集Gli1和Gli2的缺失降低了它们向少突胶质细胞的分化在这篇文章中，Samanta和同事们表明，GLI2对于成年神经干细胞中Gli1缺失介导的小鼠脑髓鞘再生的增强是必需的。
Enhancing repair of myelin is an important therapeutic goal in many neurological disorders characterized by demyelination. In the healthy adult brain, ventral neural stem cells (vNSCs) in the subventricular zone, marked by GLI1 expression, do not generate oligodendrocytes. However, in response to demyelination, their progeny are recruited to lesions where they differentiate into oligodendrocytes and ablation of GLI1 further enhances remyelination. GLI1 and GLI2 are closely related transcriptional activators but the role of GLI2 in remyelination by vNSCs is not clear. Here, we show that genetic ablation of Gli1 in vNSCs increases GLI2 expression and combined loss of both transcription factors decreases the recruitment and differentiation of their progeny in demyelinated lesions. These results indicate that GLI1 and GLI2 have distinct, non-redundant functions in vNSCs and their relative levels play an essential role in the response to demyelination. Loss of Gli1 increases GLI2 expression in SVZ neural stem cells upon demyelination Loss of Gli1 and Gli2 inhibits recruitment of neural stem cell progeny to the lesion Loss of Gli1 and Gli2 decreases their differentiation into oligodendrocytes In this article, Samanta and colleagues show that GLI2 is necessary for enhanced remyelination of the mouse brain mediated by loss of Gli1 in adult neural stem cells.
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影响因子：
3.7
作者：
Lipinski, Robert J.;Gipp, Jerry J.;Bushman, Wade
通讯作者：
Bushman, Wade
影响因子：
4.6
作者：
Savchenko, Ekaterina;Teku, Gabriel N.;Roybon, Laurent
通讯作者：
Roybon, Laurent
DOI：
10.1073/pnas.1902041116
发表时间：
2019-07-23
影响因子：
11.1
作者：
Timberlake, Andrew T.;Jin, Sheng Chih;Lifton, Richard P.
通讯作者：
Lifton, Richard P.
影响因子：
11.2
作者：
Javelaud D;Alexaki VI;Dennler S;Mohammad KS;Guise TA;Mauviel A
通讯作者：
Mauviel A
影响因子：
16.2
作者：
Ihrie RA;Shah JK;Harwell CC;Levine JH;Guinto CD;Lezameta M;Kriegstein AR;Alvarez-Buylla A
通讯作者：
Alvarez-Buylla A