title: Molecular diversity subdivides the adult forebrain neural stem cell population.
abstract: Neural stem cells (NSCs) in the ventricular domain of the subventricular zone (V-SVZ) of rodents produce neurons throughout life while those in humans become largely inactive or may be lost during infancy. Most adult NSCs are quiescent, express glial markers, and depend on Notch signaling for their self-renewal and the generation of neurons. Using genetic markers and lineage tracing, we identified subpopulations of adult V-SVZ NSCs (type 1, 2, and 3) indicating a striking heterogeneity including activated, brain lipid binding protein (BLBP, FABP7) expressing stem cells. BLBP(+) NSCs are mitotically active components of pinwheel structures in the lateral ventricle walls and persistently generate neurons in adulthood. BLBP(+) NSCs express epidermal growth factor (EGF) receptor, proliferate in response to EGF, and are a major clonogenic population in the SVZ. We also find BLBP expressed by proliferative ventricular and subventricular progenitors in the fetal and postnatal human brain. Loss of BLBP(+) stem/progenitor cells correlates with reduced neurogenesis in aging rodents and postnatal humans. These findings of molecular heterogeneity and proliferative differences subdivide the NSC population and have implications for neurogenesis in the forebrain of mammals during aging.
authors: Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Basel, Switzerland; Department of Molecular Embryology, Max Planck Institute of Immunobiology, Freiburg, Germany.
authors: Claudio
authors: C
authors: Giachino
authors: Onur
authors: O
authors: Basak
authors: Sebastian
authors: S
authors: Lugert
authors: Philip
authors: P
authors: Knuckles
authors: Kirsten
authors: K
authors: Obernier
authors: Roberto
authors: R
authors: Fiorelli
authors: Stephan
authors: S
authors: Frank
authors: Olivier
authors: O
authors: Raineteau
authors: Arturo
authors: A
authors: Alvarez-Buylla
authors: Verdon
authors: V
authors: Taylor
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction
keywords: Aging; Neural stem cells; Neurogenesis; Subventricular zone
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