title: Aberrant neural stem cell proliferation and increased adult neurogenesis in mice lacking chromatin protein HMGB2.
abstract: Neural stem and progenitor cells (NSCs/NPCs) are distinct groups of cells found in the mammalian central nervous system (CNS). Previously we determined that members of the High Mobility Group (HMG) B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2(-/-) mice exhibit SVZ hyperproliferation, increased numbers of SVZ NSCs, and a trend towards aberrant increases in newly born neurons in the olfactory bulb (OB) granule cell layer. Increases in the levels of the transcription factor p21 and the Neural cell adhesion molecule (NCAM), along with down-regulation of the transcription/pluripotency factor Oct4 in the Hmgb2-/- SVZ point to a possible pathway for this increased proliferation/differentiation. Our findings suggest that HMGB2 functions as a modulator of neurogenesis in young adult mice through regulation of NSC proliferation, and identify a potential target via which CNS repair could be amplified following trauma or disease-based neuronal degeneration.
authors.affiliation: Program in Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, New York, United States of America ; The Medical Scientist Training Program, Stony Brook University, Stony Brook, New York, United States of America ; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Ariel B
authors.initials: AB
authors.lastname: Abraham
authors.affiliation: Program in Neuroscience, Stony Brook University, Stony Brook, New York, United States of America ; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Bronstein
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Avanish S
authors.initials: AS
authors.lastname: Reddy
authors.affiliation: Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Maletic-Savatic
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Adan
authors.initials: A
authors.lastname: Aguirre
authors.affiliation: Program in Molecular and Cellular Pharmacology, Stony Brook University, Stony Brook, New York, United States of America ; Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Stella E
authors.initials: SE
authors.lastname: Tsirka
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D024261:HMGB2 Protein / Q000172:deficiency* / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D017931:DNA Primers; D024261:HMGB2 Protein