Open AccessTGFβ Lengthens the G1 Phase of Stem Cells in Aged Mouse Brain
Author(s) -
Daynac Mathieu,
Pineda Jose R.,
Chicheportiche Alexandra,
Gauthier Laurent R.,
Morizur Lise,
Boussin François D.,
Mouthon Marc-André
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1815
Subject(s) - neurogenesis , biology , neural stem cell , stem cell , microbiology and biotechnology , subventricular zone , stem cell theory of aging , cell cycle , adult stem cell , cellular differentiation , immunology , cell , haematopoiesis , stem cell factor , genetics , gene
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. S tem C ells 2014;32:3257–3265