Brg1 is required for murine neural stem cell maintenance and gliogenesis

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.

SWI/SNF Chromatin Remodeling ATPase Brm Regulates the Differentiation of Early Retinal Stem Cells/Progenitors by Influencing Brn3b Expression and Notch Signaling

“…In nonamniotic vertebrates, like frogs and fish, Brg1 has been observed to promote differentiation rather than the maintenance of stem cells/progenitors (29,30). A more recent study, using the conditional knock-out strategy, has reaffirmed the earlier observations that Brg1 maintains stem cells, whereas Brm promotes their differentiation in mammals (31). Our study demonstrates a similar role for Brm in retinal progenitors.…”

“…For example, these complexes have been shown to facilitate the differentiation of a variety of cell types such as erythrocytes (7,23), macrophages (24), myeloid cells (25), adipocytes (26), myoblasts (27), osteoblasts (28), neurons (29,30), and glia (31). Here we demonstrate the role of Brm in the differentiation of retinal progenitors into RGCs.…”

Mechanisms of ATP dependent chromatin remodeling

“…The role of SWI/SNF by all indications is far reaching. In mammals it is involved in many developmental programs such as muscle [19][20][21][22], heart [23], blood [24], skeletal [25], neuron [26][27][28][29], adipocyte [30], liver [31] and immune system/Tcell development [32,33]. Yeast SWI/SNF has been shown to be involved in an early step in homologous recombination (HR) while RSC promotes HR at the stage of strand invasion [34,35].…”

The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB–P53 pathways

“…For example, Matsumoto et al (2006) showed that BRG1 is required for murine neural stem cell maintenance and gliogenesis. No data were found on the function of BRG1 in the biology of mesenchymal stem cells (MSCs), which have a key role in the body's homeostasis.…”