In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics

Michael A. Bonaguidi, Michael A. Wheeler, Jason S. Shapiro, Ryan P. Stadel, Gerald J. Sun, Guo Li Ming, Hongjun Song

Research output: Contribution to journalArticle

Abstract

Neurogenesis and gliogenesis continue in discrete regions of the adult mammalian brain. A fundamental question remains whether cell genesis occurs from distinct lineage-restricted progenitors or from self-renewing and multipotent neural stem cells in the adult brain. Here, we developed a genetic marking strategy for lineage tracing of individual, quiescent, and nestin-expressing radial glia-like (RGL) precursors in the adult mouse dentate gyrus. Clonal analysis identified multiple modes of RGL activation, including asymmetric and symmetric self-renewal. Long-term lineage tracing in vivo revealed a significant percentage of clones that contained RGL(s), neurons, and astrocytes, indicating capacity of individual RGLs for both self-renewal and multilineage differentiation. Furthermore, conditional Pten deletion in RGLs initially promotes their activation and symmetric self-renewal but ultimately leads to terminal astrocytic differentiation and RGL depletion in the adult hippocampus. Our study identifies RGLs as self-renewing and multipotent neural stem cells and provides novel insights into in vivo properties of adult neural stem cells.

Original languageEnglish (US)
Pages (from-to)1142-1155
Number of pages14
JournalCell
Volume145
Issue number7
DOIs
StatePublished - Jun 24 2011

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Multipotent Stem Cells
Adult Stem Cells
Neural Stem Cells
Stem cells
Neuroglia
Brain
Chemical activation
Nestin
Neurogenesis
Dentate Gyrus
Astrocytes
Neurons
Hippocampus
Clone Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Bonaguidi, M. A., Wheeler, M. A., Shapiro, J. S., Stadel, R. P., Sun, G. J., Ming, G. L., & Song, H. (2011). In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell, 145(7), 1142-1155. https://doi.org/10.1016/j.cell.2011.05.024

In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. / Bonaguidi, Michael A.; Wheeler, Michael A.; Shapiro, Jason S.; Stadel, Ryan P.; Sun, Gerald J.; Ming, Guo Li; Song, Hongjun.

In: Cell, Vol. 145, No. 7, 24.06.2011, p. 1142-1155.

Research output: Contribution to journalArticle

Bonaguidi, MA, Wheeler, MA, Shapiro, JS, Stadel, RP, Sun, GJ, Ming, GL & Song, H 2011, 'In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics', Cell, vol. 145, no. 7, pp. 1142-1155. https://doi.org/10.1016/j.cell.2011.05.024
Bonaguidi MA, Wheeler MA, Shapiro JS, Stadel RP, Sun GJ, Ming GL et al. In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell. 2011 Jun 24;145(7):1142-1155. https://doi.org/10.1016/j.cell.2011.05.024
Bonaguidi, Michael A. ; Wheeler, Michael A. ; Shapiro, Jason S. ; Stadel, Ryan P. ; Sun, Gerald J. ; Ming, Guo Li ; Song, Hongjun. / In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. In: Cell. 2011 ; Vol. 145, No. 7. pp. 1142-1155.
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