首页 | 本学科首页   官方微博 | 高级检索  
     


Brg1 is required for murine neural stem cell maintenance and gliogenesis
Authors:Matsumoto Steven  Banine Fatima  Struve Jaime  Xing Rubing  Adams Chris  Liu Ying  Metzger Daniel  Chambon Pierre  Rao Mahendra S  Sherman Larry S
Affiliation:Integrative Biosciences Department, School of Dentistry, Oregon Health and Science University, Portland, 97239, USA.
Abstract:Epigenetic alterations in cell-type-specific gene expression control the transition of neural stem cells (NSCs) from predominantly neurogenic to predominantly gliogenic phases of differentiation, but how this switch occurs is unclear. Here, we show that brahma-related gene 1 (Brg1), an ATP-dependent chromatin remodeling factor, is required for the repression of neuronal commitment and the maintenance of NSCs in a state that permits them to respond to gliogenic signals. Loss of Brg1 in NSCs in conditional brg1 mutant mice results in precocious neuronal differentiation, such that cells in the ventricular zone differentiate into post-mitotic neurons before the onset of gliogenesis. As a result, there is a dramatic failure of astrocyte and oligodendrocyte differentiation in these animals. The ablation of brg1 in gliogenic progenitors in vitro also prevents growth-factor-induced astrocyte differentiation. Furthermore, proteins implicated in the maintenance of stem cells, including Sox1, Pax6 and Musashi-1, are dramatically reduced in the ventricular zones of brg1 mutant mice. We conclude that Brg1 is required to repress neuronal differentiation in NSCs as a means of permitting glial cell differentiation in response to gliogenic signals, suggesting that Brg1 regulates the switch from neurogenesis to gliogenesis.
Keywords:Neural stem cells   Brg1   Chromatin remodeling   Astrocytes   Neurons   Oligodendrocytes
本文献已被 ScienceDirect PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号