Open AccessChromatin Remodeling Factor B rg1 Supports the Early Maintenance and Late Responsiveness of N estin‐Lineage Adult Neural Stem and Progenitor Cells
Author(s) -
Petrik David,
Latchney Sarah E.,
Masiulis Irene,
Yun Sanghee,
Zhang Zilai,
Wu Jiang I.,
Eisch Amelia J.
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2215
Subject(s) - biology , nestin , neural stem cell , progenitor cell , chromatin remodeling , progenitor , stem cell , lineage (genetic) , chromatin , microbiology and biotechnology , neuroscience , genetics , gene
Insights from embryonic development suggest chromatin remodeling is important in adult neural stem cells (aNSCs) maintenance and self‐renewal, but this concept has not been fully explored in the adult brain. To assess the role of chromatin remodeling in adult neurogenesis, we inducibly deleted Brg1—the core subunit of SWI/SNF‐like Brg1/Brm‐associated factor chromatin remodeling complexes—in nestin‐expressing aNSCs and their progeny in vivo and in culture. This resulted in abnormal adult neurogenesis in the hippocampus, which initially reduced hippocampal aNSCs and progenitor maintenance, and later reduced its responsiveness to physiological stimulation. Mechanistically, deletion of Brg1 appeared to impair cell cycle progression, which is partially due to elevated p53 pathway and p21 expression. Knockdown of p53 rescued the neurosphere growth defects caused by Brg1 deletion. Our results show that epigenetic chromatin remodeling (via a Brg1 and p53/p21‐dependent process) determines the aNSCs and progenitor maintenance and responsiveness of neurogenesis. S tem C ells 2015;33:3655–3665