Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of 
Adult Neurogenesis

Kjell, Jacob; Fischer-Sternjak, Judith; Thompson, Amelia J.; Friess, Christian; Sticco, Matthew J.; Salinas, Favio; Cox, Jürgen; Martinelli, David C.; Ninkovic, Jovica; Franze, Kristian; Schiller, Herbert B.; Götz, Magdalena

doi:10.1016/j.stem.2020.01.002

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Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of Adult Neurogenesis

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Salinas, Favio
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;
Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society;

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Cox, Jürgen
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;
Cox, Jürgen / Computational Systems Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society;

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Schiller, Herbert B.
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Kjell, J., Fischer-Sternjak, J., Thompson, A. J., Friess, C., Sticco, M. J., Salinas, F., et al. (2020). Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of Adult Neurogenesis. CELL STEM CELL, 26(2), 277-293.e8. doi:10.1016/j.stem.2020.01.002.

Cite as: https://hdl.handle.net/21.11116/0000-0005-C6B0-4

Abstract

The mammalian brain contains few niches for neural stem cells (NSCs) capable of generating new neurons, whereas other regions are primarily gliogenic. Here we leverage the spatial separation of the sub-ependymal zone NSC niche and the olfactory bulb, the region to which newly generated neurons from the sub-ependymal zone migrate and integrate, and present a comprehensive proteomic characterization of these regions in comparison to the cerebral cortex, which is not conducive to neurogenesis and integration of new neurons. We find differing compositions of regulatory extracellular matrix (ECM) components in the neurogenic niche. We further show that quiescent NSCs are the main source of their local ECM, including the multi-functional enzyme transglutaminase 2, which we show is crucial for neurogenesis. Atomic force microscopy corroborated indications from the proteomic analyses that neurogenic niches are significantly stiffer than non-neurogenic parenchyma. Together these findings provide a powerful resource for unraveling unique compositions of neurogenic niches.