title: TGFβ lengthens the G1 phase of stem cells in aged mouse brain.
abstract: Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells.
authors.affiliation: CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, Fontenay-aux-Roses, France; INSERM, U967, Fontenay-aux-Roses, France; Université Paris Diderot, Sorbonne Paris Cité, UMR 967, Fontenay-aux-Roses, France; Université Paris Sud, UMR 967, Fontenay-aux-Roses, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Daynac
authors.forename: Jose R
authors.initials: JR
authors.lastname: Pineda
authors.forename: Alexandra
authors.initials: A
authors.lastname: Chicheportiche
authors.forename: Laurent R
authors.initials: LR
authors.lastname: Gauthier
authors.forename: Lise
authors.initials: L
authors.lastname: Morizur
authors.forename: François D
authors.initials: FD
authors.lastname: Boussin
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Mouthon
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D016193:G1 Phase / Q000235:genetics; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D055153:Stem Cell Niche / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta
keywords: Aging; Cell cycle; Flow cytometry; Neural stem cells; Neurogenesis; TGF-beta