Dynamic contribution of nestin-expressing stem cells to adult neurogenesis

Diane C. Lagace; Mary C. Whitman; Michele A. Noonan; Jessica L. Ables; Nathan A. DeCarolis; Amy A. Arguello; Michael H. Donovan; Stephanie J. Fischer; Laure A. Farnbauch; Robert D. Beech; Ralph J. DiLeone; Charles A. Greer; Chitra D. Mandyam; Amelia J. Eisch

doi:10.1523/JNEUROSCI.3812-07.2007

Dynamic contribution of nestin-expressing stem cells to adult neurogenesis

Diane C. Lagace, Mary C. Whitman, Michele A. Noonan, Jessica L. Ables, Nathan A. DeCarolis, Amy A. Arguello, Michael H. Donovan, Stephanie J. Fischer, Laure A. Farnbauch, Robert D. Beech, Ralph J. DiLeone, Charles A. Greer, Chitra D. Mandyam, Amelia J. Eisch

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405 Scopus citations

Abstract

Understanding the fate of adult-generated neurons and the mechanisms that influence them requires consistent labeling and tracking of large numbers of stem cells. We generated a nestin-CreER^T2/R26R-yellow fluorescent protein (YFP) mouse to inducibly label nestin-expressing stem cells and their progeny in the adult subventricular zone (SVZ) and subgranular zone (SGZ). Several findings show that the estrogen ligand tamoxifen (TAM) specifically induced recombination in stem cells and their progeny in nestin-CreER ^T2/R26R-YFP mice: 97% of SGZ stem-like cells (GFAP/Sox2 with radial glial morphology) expressed YFP; YFP+ neurospheres could be generated in vitro after recombination in vivo, and maturing YFP+ progeny were increasingly evident in the olfactory bulb (OB) and dentate gyrus (DG) granule cell layer. Revealing an unexpected regional dissimilarity in adult neurogenesis, YFP+ cells accumulated up to 100 d after TAMin the OB, but in the SGZ, YFP+ cells reached a plateau 30 d after TAM. In addition, most SVZ and SGZ YFP+ cells became neurons, underscoring a link between nestin and neuronal fate. Finally, quantification of YFP+ cells in nestin-CreER^T2/R26R-YFP mice allowed us to estimate, for example, that stem cells and their progeny contribute to no more than 1% of the adult DG granule cell layer. In addition to revealing the dynamic contribution of nestin-expressing stem cells to adult neurogenesis, this work highlights the utility of the nestin-CreER^T2/R26R-YFP mouse for inducible gene ablation in stem cells and their progeny in vivo in the two major regions of adult neurogenesis.

Original language	English (US)
Pages (from-to)	12623-12629
Number of pages	7
Journal	Journal of Neuroscience
Volume	27
Issue number	46
DOIs	https://doi.org/10.1523/JNEUROSCI.3812-07.2007
State	Published - Nov 14 2007

Keywords

Dentate gyrus
Olfactory bulb
Rostral migratory stream
Subgranular zone
Subventricular zone
Tamoxifen

ASJC Scopus subject areas

General Neuroscience

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10.1523/JNEUROSCI.3812-07.2007

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Lagace, D. C., Whitman, M. C., Noonan, M. A., Ables, J. L., DeCarolis, N. A., Arguello, A. A., Donovan, M. H., Fischer, S. J., Farnbauch, L. A., Beech, R. D., DiLeone, R. J., Greer, C. A., Mandyam, C. D., & Eisch, A. J. (2007). Dynamic contribution of nestin-expressing stem cells to adult neurogenesis. Journal of Neuroscience, 27(46), 12623-12629. https://doi.org/10.1523/JNEUROSCI.3812-07.2007

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title = "Dynamic contribution of nestin-expressing stem cells to adult neurogenesis",

abstract = "Understanding the fate of adult-generated neurons and the mechanisms that influence them requires consistent labeling and tracking of large numbers of stem cells. We generated a nestin-CreERT2/R26R-yellow fluorescent protein (YFP) mouse to inducibly label nestin-expressing stem cells and their progeny in the adult subventricular zone (SVZ) and subgranular zone (SGZ). Several findings show that the estrogen ligand tamoxifen (TAM) specifically induced recombination in stem cells and their progeny in nestin-CreER T2/R26R-YFP mice: 97% of SGZ stem-like cells (GFAP/Sox2 with radial glial morphology) expressed YFP; YFP+ neurospheres could be generated in vitro after recombination in vivo, and maturing YFP+ progeny were increasingly evident in the olfactory bulb (OB) and dentate gyrus (DG) granule cell layer. Revealing an unexpected regional dissimilarity in adult neurogenesis, YFP+ cells accumulated up to 100 d after TAMin the OB, but in the SGZ, YFP+ cells reached a plateau 30 d after TAM. In addition, most SVZ and SGZ YFP+ cells became neurons, underscoring a link between nestin and neuronal fate. Finally, quantification of YFP+ cells in nestin-CreERT2/R26R-YFP mice allowed us to estimate, for example, that stem cells and their progeny contribute to no more than 1% of the adult DG granule cell layer. In addition to revealing the dynamic contribution of nestin-expressing stem cells to adult neurogenesis, this work highlights the utility of the nestin-CreERT2/R26R-YFP mouse for inducible gene ablation in stem cells and their progeny in vivo in the two major regions of adult neurogenesis.",

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author = "Lagace, {Diane C.} and Whitman, {Mary C.} and Noonan, {Michele A.} and Ables, {Jessica L.} and DeCarolis, {Nathan A.} and Arguello, {Amy A.} and Donovan, {Michael H.} and Fischer, {Stephanie J.} and Farnbauch, {Laure A.} and Beech, {Robert D.} and DiLeone, {Ralph J.} and Greer, {Charles A.} and Mandyam, {Chitra D.} and Eisch, {Amelia J.}",

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T1 - Dynamic contribution of nestin-expressing stem cells to adult neurogenesis

AU - Lagace, Diane C.

AU - Whitman, Mary C.

AU - Noonan, Michele A.

AU - Ables, Jessica L.

AU - DeCarolis, Nathan A.

AU - Arguello, Amy A.

AU - Donovan, Michael H.

AU - Fischer, Stephanie J.

AU - Farnbauch, Laure A.

AU - Beech, Robert D.

AU - DiLeone, Ralph J.

AU - Greer, Charles A.

AU - Mandyam, Chitra D.

AU - Eisch, Amelia J.

PY - 2007/11/14

Y1 - 2007/11/14

N2 - Understanding the fate of adult-generated neurons and the mechanisms that influence them requires consistent labeling and tracking of large numbers of stem cells. We generated a nestin-CreERT2/R26R-yellow fluorescent protein (YFP) mouse to inducibly label nestin-expressing stem cells and their progeny in the adult subventricular zone (SVZ) and subgranular zone (SGZ). Several findings show that the estrogen ligand tamoxifen (TAM) specifically induced recombination in stem cells and their progeny in nestin-CreER T2/R26R-YFP mice: 97% of SGZ stem-like cells (GFAP/Sox2 with radial glial morphology) expressed YFP; YFP+ neurospheres could be generated in vitro after recombination in vivo, and maturing YFP+ progeny were increasingly evident in the olfactory bulb (OB) and dentate gyrus (DG) granule cell layer. Revealing an unexpected regional dissimilarity in adult neurogenesis, YFP+ cells accumulated up to 100 d after TAMin the OB, but in the SGZ, YFP+ cells reached a plateau 30 d after TAM. In addition, most SVZ and SGZ YFP+ cells became neurons, underscoring a link between nestin and neuronal fate. Finally, quantification of YFP+ cells in nestin-CreERT2/R26R-YFP mice allowed us to estimate, for example, that stem cells and their progeny contribute to no more than 1% of the adult DG granule cell layer. In addition to revealing the dynamic contribution of nestin-expressing stem cells to adult neurogenesis, this work highlights the utility of the nestin-CreERT2/R26R-YFP mouse for inducible gene ablation in stem cells and their progeny in vivo in the two major regions of adult neurogenesis.

AB - Understanding the fate of adult-generated neurons and the mechanisms that influence them requires consistent labeling and tracking of large numbers of stem cells. We generated a nestin-CreERT2/R26R-yellow fluorescent protein (YFP) mouse to inducibly label nestin-expressing stem cells and their progeny in the adult subventricular zone (SVZ) and subgranular zone (SGZ). Several findings show that the estrogen ligand tamoxifen (TAM) specifically induced recombination in stem cells and their progeny in nestin-CreER T2/R26R-YFP mice: 97% of SGZ stem-like cells (GFAP/Sox2 with radial glial morphology) expressed YFP; YFP+ neurospheres could be generated in vitro after recombination in vivo, and maturing YFP+ progeny were increasingly evident in the olfactory bulb (OB) and dentate gyrus (DG) granule cell layer. Revealing an unexpected regional dissimilarity in adult neurogenesis, YFP+ cells accumulated up to 100 d after TAMin the OB, but in the SGZ, YFP+ cells reached a plateau 30 d after TAM. In addition, most SVZ and SGZ YFP+ cells became neurons, underscoring a link between nestin and neuronal fate. Finally, quantification of YFP+ cells in nestin-CreERT2/R26R-YFP mice allowed us to estimate, for example, that stem cells and their progeny contribute to no more than 1% of the adult DG granule cell layer. In addition to revealing the dynamic contribution of nestin-expressing stem cells to adult neurogenesis, this work highlights the utility of the nestin-CreERT2/R26R-YFP mouse for inducible gene ablation in stem cells and their progeny in vivo in the two major regions of adult neurogenesis.

KW - Dentate gyrus

KW - Olfactory bulb

KW - Rostral migratory stream

KW - Subgranular zone

KW - Subventricular zone

KW - Tamoxifen

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JO - Journal of Neuroscience

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Dynamic contribution of nestin-expressing stem cells to adult neurogenesis

Abstract

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