Chromatin Remodeling Factor Brg1 Supports the Early Maintenance and Late Responsiveness of Nestin-Lineage Adult Neural Stem and Progenitor Cells. (9th October 2015)

• Record Type: Journal Article
• Authors: Petrik, David; Latchney, Sarah E.; Masiulis, Irene; Yun, Sanghee; Zhang, Zilai; Wu, Jiang I.; Eisch, Amelia J.
• Is Part Of: Stem cells. Volume 33:Number 12(2015:Dec.)
• Page Start: 3655
• Page End: 3665
• Publication Date: 2015-10-09
• Subjects: Neural stem cell -- Adult stem cell -- Cellular proliferation -- Cre-loxP system -- Flow cytometry -- Epigenetics -- Nervous system -- Transgenic mouse; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2215
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: 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. Stem Cells 2015;33:3655–3665