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Cover ArticleFeatured ArticleArticles, Development/Plasticity/Repair

Purification of Neural Precursor Cells Reveals the Presence of Distinct, Stimulus-Specific Subpopulations of Quiescent Precursors in the Adult Mouse Hippocampus

Dhanisha J. Jhaveri, Imogen O'Keeffe, Gregory J. Robinson, Qiong-Yi Zhao, Zong Hong Zhang, Virginia Nink, Ramesh K. Narayanan, Geoffrey W. Osborne, Naomi R. Wray and Perry F. Bartlett
Journal of Neuroscience 27 May 2015, 35 (21) 8132-8144; https://doi.org/10.1523/JNEUROSCI.0504-15.2015
Dhanisha J. Jhaveri
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Imogen O'Keeffe
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Gregory J. Robinson
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Qiong-Yi Zhao
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Zong Hong Zhang
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Virginia Nink
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Ramesh K. Narayanan
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Geoffrey W. Osborne
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Naomi R. Wray
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Perry F. Bartlett
The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia
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Abstract

The activity of neural precursor cells in the adult hippocampus is regulated by various stimuli; however, whether these stimuli regulate the same or different precursor populations remains unknown. Here, we developed a novel cell-sorting protocol that allows the purification to homogeneity of neurosphere-forming neural precursors from the adult mouse hippocampus and examined the responsiveness of individual precursors to various stimuli using a clonal assay. We show that within the Hes5-GFP+/Nestin-GFP+/EGFR+ cell population, which comprises the majority of neurosphere-forming precursors, there are two distinct subpopulations of quiescent precursor cells, one directly activated by high-KCl depolarization, and the other activated by norepinephrine (NE). We then demonstrate that these two populations are differentially distributed along the septotemporal axis of the hippocampus, and show that the NE-responsive precursors are selectively regulated by GABA, whereas the KCl-responsive precursors are selectively modulated by corticosterone. Finally, based on RNAseq analysis by deep sequencing, we show that the progeny generated by activating NE-responsive versus KCl-responsive quiescent precursors are molecularly different. These results demonstrate that the adult hippocampus contains phenotypically similar but stimulus-specific populations of quiescent precursors, which may give rise to neural progeny with different functional capacity.

  • adult neurogenesis
  • hippocampus
  • neural precursor cells
  • neural stem cells
  • norepinephrine
  • quiescent
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The Journal of Neuroscience: 35 (21)
Journal of Neuroscience
Vol. 35, Issue 21
27 May 2015
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Purification of Neural Precursor Cells Reveals the Presence of Distinct, Stimulus-Specific Subpopulations of Quiescent Precursors in the Adult Mouse Hippocampus
Dhanisha J. Jhaveri, Imogen O'Keeffe, Gregory J. Robinson, Qiong-Yi Zhao, Zong Hong Zhang, Virginia Nink, Ramesh K. Narayanan, Geoffrey W. Osborne, Naomi R. Wray, Perry F. Bartlett
Journal of Neuroscience 27 May 2015, 35 (21) 8132-8144; DOI: 10.1523/JNEUROSCI.0504-15.2015

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Purification of Neural Precursor Cells Reveals the Presence of Distinct, Stimulus-Specific Subpopulations of Quiescent Precursors in the Adult Mouse Hippocampus
Dhanisha J. Jhaveri, Imogen O'Keeffe, Gregory J. Robinson, Qiong-Yi Zhao, Zong Hong Zhang, Virginia Nink, Ramesh K. Narayanan, Geoffrey W. Osborne, Naomi R. Wray, Perry F. Bartlett
Journal of Neuroscience 27 May 2015, 35 (21) 8132-8144; DOI: 10.1523/JNEUROSCI.0504-15.2015
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Keywords

  • adult neurogenesis
  • hippocampus
  • neural precursor cells
  • neural stem cells
  • norepinephrine
  • quiescent

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