Prospective identification, isolation, and profiling of a telomerase-expressing subpopulation of human neural stem cells, using sox2 enhancer-directed fluorescence-activated cell sorting

Su Wang, Devin Chandler-Militello, Gang Lu, Neeta Roy, Alex Zielke, Romane Auvergne, Nancy Stanwood, Daniel Geschwind, Giovanni Coppola, Silvia K. Nicolis, Fraser J. Sim, Steven A. Goldman

Research output: Contribution to journalArticle

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Abstract

Sox2 is expressed by neural stem and progenitor cells, and a sox2 enhancer identifies these cells in the forebrains of both fetal and adult transgenic mouse reporters. We found that an adenovirus encoding EGFP placed under the regulatory control of a 0.4 kb sox2 core enhancer selectively identified multipotential and self-renewing neural progenitor cells in dissociates of human fetal forebrain. Upon EGFP-based fluorescence-activated cell sorting (FACS), the E/sox2:EGFP+ isolates were propagable for up to 1 year in vitro, and remained multilineage competent throughout. E/sox2:EGFP+ cells expressed more telomerase enzymatic activity than matched E/sox2:EGFP-depleted populations, and maintained their telomeric lengths with successive passage. Gene expression analysis of E/sox2:EGFP-sorted neural progenitor cells, normalized to the unsorted forebrain dissociates from which they derived, revealed marked overexpression of genes within the notch and wnt pathways, and identified multiple elements of each pathway that appear selective to human neural progenitors. Sox2 enhancer-based FACS thus permits the prospective identification and direct isolation of a telomerase-active population of neural stem cells from the human fetal forebrain, and the elucidation of both the transcriptome and dominant signaling pathways of these critically important cells.

Original languageEnglish (US)
Pages (from-to)14635-14648
Number of pages14
JournalJournal of Neuroscience
Volume30
Issue number44
DOIs
StatePublished - Nov 3 2010

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Neural Stem Cells
Telomerase
Prosencephalon
Flow Cytometry
Stem Cells
Wnt Signaling Pathway
Transcriptome
Adenoviridae
Transgenic Mice
Population
Gene Expression
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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Prospective identification, isolation, and profiling of a telomerase-expressing subpopulation of human neural stem cells, using sox2 enhancer-directed fluorescence-activated cell sorting. / Wang, Su; Chandler-Militello, Devin; Lu, Gang; Roy, Neeta; Zielke, Alex; Auvergne, Romane; Stanwood, Nancy; Geschwind, Daniel; Coppola, Giovanni; Nicolis, Silvia K.; Sim, Fraser J.; Goldman, Steven A.

In: Journal of Neuroscience, Vol. 30, No. 44, 03.11.2010, p. 14635-14648.

Research output: Contribution to journalArticle

Wang, S, Chandler-Militello, D, Lu, G, Roy, N, Zielke, A, Auvergne, R, Stanwood, N, Geschwind, D, Coppola, G, Nicolis, SK, Sim, FJ & Goldman, SA 2010, 'Prospective identification, isolation, and profiling of a telomerase-expressing subpopulation of human neural stem cells, using sox2 enhancer-directed fluorescence-activated cell sorting', Journal of Neuroscience, vol. 30, no. 44, pp. 14635-14648. https://doi.org/10.1523/JNEUROSCI.1729-10.2010
Wang, Su ; Chandler-Militello, Devin ; Lu, Gang ; Roy, Neeta ; Zielke, Alex ; Auvergne, Romane ; Stanwood, Nancy ; Geschwind, Daniel ; Coppola, Giovanni ; Nicolis, Silvia K. ; Sim, Fraser J. ; Goldman, Steven A. / Prospective identification, isolation, and profiling of a telomerase-expressing subpopulation of human neural stem cells, using sox2 enhancer-directed fluorescence-activated cell sorting. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 44. pp. 14635-14648.
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