TGFβ Lengthens the G1 Phase of Stem Cells in Aged Mouse Brain (original) (raw)

Journal Article

,

a

CEA DSV iRCM SCSR Laboratoire de Radiopathologie

, Fontenay-aux-Roses,

France

b

INSERM, U967

, Fontenay-aux-Roses,

France

c

Université Paris Diderot Sorbonne Paris Cité, UMR 967

, Fontenay-aux-Roses,

France

d

Université Paris Sud, UMR 967

, Fontenay-aux-Roses,

France

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,

a

CEA DSV iRCM SCSR Laboratoire de Radiopathologie

, Fontenay-aux-Roses,

France

b

INSERM, U967

, Fontenay-aux-Roses,

France

c

Université Paris Diderot Sorbonne Paris Cité, UMR 967

, Fontenay-aux-Roses,

France

d

Université Paris Sud, UMR 967

, Fontenay-aux-Roses,

France

Search for other works by this author on:

,

a

CEA DSV iRCM SCSR Laboratoire de Radiopathologie

, Fontenay-aux-Roses,

France

b

INSERM, U967

, Fontenay-aux-Roses,

France

c

Université Paris Diderot Sorbonne Paris Cité, UMR 967

, Fontenay-aux-Roses,

France

d

Université Paris Sud, UMR 967

, Fontenay-aux-Roses,

France

Search for other works by this author on:

,

a

CEA DSV iRCM SCSR Laboratoire de Radiopathologie

, Fontenay-aux-Roses,

France

b

INSERM, U967

, Fontenay-aux-Roses,

France

c

Université Paris Diderot Sorbonne Paris Cité, UMR 967

, Fontenay-aux-Roses,

France

d

Université Paris Sud, UMR 967

, Fontenay-aux-Roses,

France

Search for other works by this author on:

,

a

CEA DSV iRCM SCSR Laboratoire de Radiopathologie

, Fontenay-aux-Roses,

France

b

INSERM, U967

, Fontenay-aux-Roses,

France

c

Université Paris Diderot Sorbonne Paris Cité, UMR 967

, Fontenay-aux-Roses,

France

d

Université Paris Sud, UMR 967

, Fontenay-aux-Roses,

France

Search for other works by this author on:

,

a

CEA DSV iRCM SCSR Laboratoire de Radiopathologie

, Fontenay-aux-Roses,

France

b

INSERM, U967

, Fontenay-aux-Roses,

France

c

Université Paris Diderot Sorbonne Paris Cité, UMR 967

, Fontenay-aux-Roses,

France

d

Université Paris Sud, UMR 967

, Fontenay-aux-Roses,

France

Correspondence: Marc-André Mouthon, Ph.D., CEA, DSV, iRCM, SCSR, Laboratoire de Radiopathologie, BP n°6, 92265 Fontenay-aux-Roses cedex, France. Telephone: 33-1-46-54-94-61; Fax: 33-1-46–54-91-80; e-mail: marc-andre.mouthon@cea.fr

Search for other works by this author on:

a

CEA DSV iRCM SCSR Laboratoire de Radiopathologie

, Fontenay-aux-Roses,

France

b

INSERM, U967

, Fontenay-aux-Roses,

France

c

Université Paris Diderot Sorbonne Paris Cité, UMR 967

, Fontenay-aux-Roses,

France

d

Université Paris Sud, UMR 967

, Fontenay-aux-Roses,

France

Correspondence: Marc-André Mouthon, Ph.D., CEA, DSV, iRCM, SCSR, Laboratoire de Radiopathologie, BP n°6, 92265 Fontenay-aux-Roses cedex, France. Telephone: 33-1-46-54-94-61; Fax: 33-1-46–54-91-80; e-mail: marc-andre.mouthon@cea.fr

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Received:

21 February 2014

Published:

26 November 2014

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Mathieu Daynac, Jose R. Pineda, Alexandra Chicheportiche, Laurent R. Gauthier, Lise Morizur, François D. Boussin, Marc-André Mouthon, TGF_β_ Lengthens the G1 Phase of Stem Cells in Aged Mouse Brain, Stem Cells, Volume 32, Issue 12, December 2014, Pages 3257–3265, https://doi.org/10.1002/stem.1815
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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 TGF_β_ 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_β_ regenerative therapies based on stimulating endogenous neural stem cells. Stem Cells 2014;32:3257–3265

© 2014 AlphaMed Press

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