4.7 Article

TGFβ Lengthens the G1 Phase of Stem Cells in Aged Mouse Brain

Journal

STEM CELLS
Volume 32, Issue 12, Pages 3257-3265

Publisher

WILEY
DOI: 10.1002/stem.1815

Keywords

Neural stem cells; Neurogenesis; Cell cycle; Flow cytometry; Aging; TGF-beta

Funding

  1. ANR-SEST (Neurorad)
  2. INCA (Tetratips) [PLBIO10-030]
  3. Electricite de France (EDF)
  4. La Ligue Contre le Cancer
  5. Fondation de France [Engt: 2013-00042632]
  6. Region Ile-de-France (DIM Biotherapies)

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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 TGF 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-TGF regenerative therapies based on stimulating endogenous neural stem cells. Stem Cells2014;32:3257-3265

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