title: Purification of neural precursor cells reveals the presence of distinct, stimulus-specific subpopulations of quiescent precursors in the adult mouse hippocampus.
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.
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia dhanisha@uq.edu.au p.bartlett@uq.edu.au.
authors.forename: Dhanisha J
authors.initials: DJ
authors.lastname: Jhaveri
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia.
authors.forename: Imogen
authors.initials: I
authors.lastname: O'Keeffe
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Robinson
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia.
authors.forename: Qiong-Yi
authors.identifier: http://orcid.org/0000-0002-6341-0416
authors.initials: QY
authors.lastname: Zhao
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia.
authors.forename: Zong Hong
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia.
authors.forename: Virginia
authors.initials: V
authors.lastname: Nink
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Narayanan
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Osborne
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia.
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Wray
authors.affiliation: The University of Queensland, Queensland Brain Institute, Brisbane 4072, Queensland, Australia dhanisha@uq.edu.au p.bartlett@uq.edu.au.
authors.forename: Perry F
authors.initials: PF
authors.lastname: Bartlett
mesh_terms: D000367:Age Factors; D000818:Animals; D002452:Cell Count / Q000379:methods; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*
keywords: adult neurogenesis; hippocampus; neural precursor cells; neural stem cells; norepinephrine; quiescent