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Fast clonal expansion and limited neural stem cell self-renewal in the adult subependymal zone

Nature Neuroscience volume 18, pages 490492 (2015) | Download Citation

Abstract

We analyzed the progeny of individual neural stem cells (NSCs) of the mouse adult subependymal zone (SEZ) in vivo and found a markedly fast lineage amplification, as well as limited NSC self-renewal and exhaustion in a few weeks. We further unraveled the mechanisms of neuronal subtype generation, finding that a higher proportion of NSCs were dedicated to generate deep granule cells in the olfactory bulb and that larger clones were produced by these NSCs.

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Acknowledgements

We foremost would like to thank H. Clevers and H. Snippert for the Confetti mouse line. In addition, we are thankful to T. Özturk for excellent technical help and L. Dimou, A. Saghatelyan, S. Stricker and P. Malatesta for critical reading of the manuscript. We also gratefully acknowledge funding to J.N. from the German Research foundation (DFG) by the SFB 870 and SPP 1392 and to M.G. from the German Research foundation (DFG) by the SFB 870, Gö 640/11-1, the Munich Cluster for Systems Neurology (EXC 1010 SyNergy), the Helmholtz Foundation by the ICEMED Alliance and the European Research Council by an ERC Advanced Grant.

Author information

Author notes

    • Magdalena Götz
    •  & Jovica Ninkovic

    These authors contributed equally to this work.

Affiliations

  1. Institute of Stem Cell Research, Helmholtz Center, Munich, Germany.

    • Filippo Calzolari
    • , Julia Michel
    • , Emily Violette Baumgart
    • , Magdalena Götz
    •  & Jovica Ninkovic
  2. Biomedical Center, University of Munich, Munich, Germany.

    • Filippo Calzolari
    • , Magdalena Götz
    •  & Jovica Ninkovic
  3. Institute of Computational Biology, Helmholtz Center, Munich, Germany.

    • Fabian Theis
  4. Institute for Mathematical Sciences, Technical University Munich, Garching, Germany.

    • Fabian Theis
  5. Munich cluster for Systems Neurology (SYNERGY), Ludwig-Maximilians-Universität, München, Germany.

    • Magdalena Götz
    •  & Jovica Ninkovic

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Contributions

F.C., J.M., J.N. and M.G. designed the experiments. F.C. and J.M. performed the experiments and analyzed data. E.V.B. provided technical assistance. F.T. performed mathematical modeling. F.C., J.N. and M.G. wrote the manuscript, to which F.T. contributed the mathematical modeling method section. All of the authors critically read and contributed comments to the final version of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Magdalena Götz or Jovica Ninkovic.

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Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–3 and Supplementary Table 1

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    Supplementary Methods Checklist

Excel files

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    Supplementary Table 2

    Summary of all observed clones at different time points after the TM induction.

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DOI

https://doi.org/10.1038/nn.3963