Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Cell stem cell, 2020-02, Vol.26 (2), p.277-293.e8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] •Proteomics define the NSC niche-specific extracellular matrix•Detergent-solubility profiling reveals extracellular matrix architecture•Transglutaminase 2 regulates neurogenesis•Stiffness is increased in the neurogenic niches of the brain The physical properties of stem cell niches are thought to mediate important regulatory functions. Here we provide a proteomic resource of the neural stem cell niche in comparison to gliogenic brain parenchyma, highlighting stiffness and the enzyme transglutaminase 2 as key regulators of neurogenesis.