title: In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis.
abstract: Neural stem cells and neurogenesis persist in the adult mammalian brain subventricular zone (SVZ). Cells born in the rodent SVZ migrate to the olfactory bulb (Ob) where they differentiate into interneurons. To determine the gene expression and functional profile of SVZ neurogenesis, we performed three complementary sets of transcriptional analysis experiments using Affymetrix GeneChips: (1) comparison of adult mouse SVZ and Ob gene expression profiles with those of the striatum, cerebral cortex, and hippocampus; (2) profiling of SVZ stem cells and ependyma isolated by fluorescent-activated cell sorting (FACS); and (3) analysis of gene expression changes during in vivo SVZ regeneration after anti-mitotic treatment. Gene Ontology (GO) analysis of data from these three separate approaches showed that in adult SVZ neurogenesis, RNA splicing and chromatin remodeling are biological processes as statistically significant as cell proliferation, transcription, and neurogenesis. In non-neurogenic brain regions, RNA splicing and chromatin remodeling were not prominent processes. Fourteen mRNA splicing factors including Sf3b1, Sfrs2, Lsm4, and Khdrbs1/Sam68 were detected along with 9 chromatin remodeling genes including Mll, Bmi1, Smarcad1, Baf53a, and Hat1. We validated the transcriptional profile data with Northern blot analysis and in situ hybridization. The data greatly expand the catalogue of cell cycle components, transcription factors, and migration genes for adult SVZ neurogenesis and reveal RNA splicing and chromatin remodeling as prominent biological processes for these germinal cells.
authors.affiliation: Department of Neurological Surgery and Developmental and Stem Cell Biology Program, University of California, San Francisco, CA 94143, USA. limd@neurosurg.ucsf.edu
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lim
authors.forename: Mayte
authors.initials: M
authors.lastname: Suárez-Fariñas
authors.forename: Felix
authors.initials: F
authors.lastname: Naef
authors.forename: Coleen R
authors.initials: CR
authors.lastname: Hacker
authors.forename: Benedicte
authors.initials: B
authors.lastname: Menn
authors.forename: Hirohide
authors.initials: H
authors.lastname: Takebayashi
authors.forename: Marcelo
authors.initials: M
authors.lastname: Magnasco
authors.forename: Nila
authors.initials: N
authors.lastname: Patil
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
mesh_terms: D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D002843:Chromatin / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D017931:DNA Primers; D005434:Flow Cytometry; D008322:Mammals; D009419:Nerve Tissue Proteins / Q000235:genetics; D009420:Nervous System / Q000254:growth & development; D012326:RNA Splicing / Q000235:genetics*; D051381:Rats; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D017931:DNA Primers; D009419:Nerve Tissue Proteins