title: Chromatin Remodeling Factor Brg1 Supports the Early Maintenance and Late Responsiveness of Nestin-Lineage Adult Neural Stem and Progenitor Cells.
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.
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: David
authors.initials: D
authors.lastname: Petrik
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Latchney
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Masiulis
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Sanghee
authors.initials: S
authors.lastname: Yun
authors.affiliation: Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Zilai
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Jiang I
authors.initials: JI
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Amelia J
authors.initials: AJ
authors.lastname: Eisch
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D064231:Nestin / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: C577485:Nes protein, mouse; D064231:Nestin; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C513194:Smarca4 protein, mouse; D004265:DNA Helicases
keywords: Adult stem cell; Cellular proliferation; Cre-loxP system; Epigenetics; Flow cytometry; Nervous system; Neural stem cell; Transgenic mouse