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Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain1. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis2, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism3,4,5, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA6, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation.

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Change history

  • 09 January 2013

    The accession number in the original PDF was corrected.


Primary accessions

Gene Expression Omnibus

Data deposits

Microarray data are deposited in the Gene Expression Omnibus under accession number GSE27391.


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We thank S. Aigner, D. C. Lie, F. H. Gage and members of the Jessberger group for conceptual input; S. Kobel, C. Fischer, K. Walter, P. Sidiropoulos, T. Buch, B. Becher, P. Pelczar, P. Lötscher, A. J. Eisch and D. C. Lagace for experimental help or reagents; and the Light Microscopy and Screening Center (LMSC) of the ETH Zurich and the BioImaging and Optics Platform (BIOP) of the EPFL for help with imaging. This study was supported by the NCCR Neural Plasticity and Repair, Swiss National Science Foundation, TH grant (ETH-01 08-1), Zurich Neuroscience Center (ZNZ), Novartis Foundation, Theodore Ott Foundation, and the EMBO Young Investigator program (to S.J.). M.K. was supported by the Janggen-Pöhn foundation.

Author information

Author notes

    • Marlen Knobloch
    •  & Simon M. G. Braun

    These authors contributed equally to this work.


  1. Brain Research Institute, Faculty of Medicine, University of Zurich, 8057 Zurich, Switzerland

    • Marlen Knobloch
    • , Simon M. G. Braun
    • , Raquel A. C. Machado
    •  & Sebastian Jessberger
  2. Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology (ETH) Zurich, 8093 Zurich, Switzerland

    • Marlen Knobloch
    • , Simon M. G. Braun
    • , Luis Zurkirchen
    • , Carolin von Schoultz
    • , Werner J. Kovacs
    • , Özlem Karalay
    • , Ueli Suter
    • , Raquel A. C. Machado
    •  & Sebastian Jessberger
  3. Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland

    • Nicola Zamboni
  4. Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany

    • Marcos J. Araúzo-Bravo
  5. Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland

    • Marta Roccio
    •  & Matthias P. Lutolf
  6. Washington University School of Medicine, Division of Endocrinology, Metabolism & Lipid Research, St. Louis, Missouri 63110, USA

    • Clay F. Semenkovich


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M.K. contributed to the concept, carried out experiments, analysed data and co-wrote the paper. S.M.G.B. carried out experiments and analysed data. L.Z., C.v.S. and R.A.C.M. carried out experiments. N.Z. carried out the metabolomics experiments. M.J.A.B. analysed the array data. M.R. and M.P.L. contributed to the time-lapse imaging of NSPCs. W.J.K. contributed to the lipid metabolism experiments. Ö.K., U.S. and C.F.S. provided reagents. All authors revised the manuscript. S.J. developed the concept and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Sebastian Jessberger.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Figures 1-12, a Supplementary Discussion, Supplementary Methods and Supplementary References.

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    Supplementary Tables

    This file contains Supplementary Tables 1-6.


  1. 1.

    Video 1: Single-cell imaging of Spot14+ NSPC in vitro (example 1)

    Shown is a time lapse imaging of a single Spot14 positive NSPC captured in a hydrogel-based microwell over 81h. The cell is alive throughout the time observed but does not divide, illustrating the more quiescent nature of Spot14 positive NSPCs

  2. 2.

    Video 2: Single-cell imaging of Spot14+ NSPC in vitro (example 2)

    Shown is a time lapse imaging of a single Spot14 positive NSPC captured in a hydrogel-based microwell over 81h. The cell is alive throughout the time observed but does not divide.

  3. 3.

    Video 3: Single-cell imaging of Spot14- NSPC in vitro (example 1)

    Shown is a time lapse imaging of a single Spot14 negative NSPC captured in a hydrogel-based microwell over 81h. The cell is dividing several times throughout the time observed, illustrating the more proliferative nature of Spot14 negative NSPCs compared to Spot14 positive NSPCs.

  4. 4.

    Video 4: Single-cell imaging of Spot14- NSPC in vitro (example 2)

    Shown is a time lapse imaging of a single Spot14 negative NSPC captured in a hydrogel-based microwell over 81h. The cell is dividing several times throughout the time observed.

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