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PMID: 18003841 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 27 ·No. 46 ·2007-11-14 ·Pages 12623-9

Lagace DC, Whitman MC, Noonan MA, Ables JL, DeCarolis NA, Arguello AA, Donovan MH, Fischer SJ, Farnbauch LA, Beech RD, DiLeone RJ, Greer CA, Mandyam CD, Eisch AJ

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 TAM in 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.

MeSH Terms
Animals Brain/cytology,metabolism Cell Differentiation/drug effects,physiology Cell Lineage/drug effects,physiology Cell Proliferation/drug effects Dentate Gyrus/cytology,metabolism Gene Targeting/methods Intermediate Filament Proteins/metabolism Luminescent Proteins/genetics,metabolism Mice Mice, Transgenic Models, Animal Nerve Regeneration/drug effects,physiology Nerve Tissue Proteins/metabolism Nestin Neuroglia/cytology,drug effects,metabolism Neurons/metabolism Olfactory Bulb/cytology,metabolism Recombinant Fusion Proteins/genetics,metabolism Recombination, Genetic/drug effects,genetics Selective Estrogen Receptor Modulators/pharmacology Stem Cells/drug effects,metabolism Tamoxifen/pharmacology
Chemicals
Intermediate Filament Proteins Luminescent Proteins Nerve Tissue Proteins Nes protein, mouse Nestin Recombinant Fusion Proteins Selective Estrogen Receptor Modulators Tamoxifen
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Lagace Diane C
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.
Whitman Mary C
Noonan Michele A
Ables Jessica L
DeCarolis Nathan A
Arguello Amy A
Donovan Michael H
Fischer Stephanie J
Farnbauch Laure A
Beech Robert D
DiLeone Ralph J
Greer Charles A
Mandyam Chitra D
Eisch Amelia J
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.3812-07.2007
Published
2007-11-14
Pages
12623-9
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC3718551
Subset
IM
Grants
NIDA NIH HHS · R01 DA016765 · United States
NIDA NIH HHS · F32 DA018017 · United States
NIDCD NIH HHS · DC00213 · United States
NIDCD NIH HHS · DC006972 · United States
NIDCD NIH HHS · R01 DC000210 · United States
NIDA NIH HHS · DA16765-02S1 · United States
NIGMS NIH HHS · T32 GM007205 · United States
NIDCD NIH HHS · R01 DC006972 · United States
NIDCD NIH HHS · F32 DC000210 · United States
NIDA NIH HHS · DA016765 · United States
NIDA NIH HHS · T32 DA007290 · United States
NIDA NIH HHS · DA018017 · United States
NIMH NIH HHS · MH754572 · United States
NIDA NIH HHS · DA07290 · United States
NIGMS NIH HHS · GM07205 · United States
NIMH NIH HHS · F31 MH075457 · United States
NIDA NIH HHS · K02 DA023555 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.3812-07.2007 PMC Full Text View journal details
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