Chromatin Remodeling Factor Brg1 Supports the Early Maintenance and Late Responsiveness of Nestin-Lineage Adult Neural Stem and Progenitor Cells

David Petrik, Sarah E. Latchney, Irene Masiulis, Sanghee Yun, Zilai Zhang, Jiang I. Wu, Amelia J. Eisch

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3655-3665
Number of pages11
JournalStem Cells
Volume33
Issue number12
DOIs
StatePublished - Dec 1 2015

Keywords

  • Adult stem cell
  • Cellular proliferation
  • Cre-loxP system
  • Epigenetics
  • Flow cytometry
  • Nervous system
  • Neural stem cell
  • Transgenic mouse

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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