Comprehensive proteome of the adult neural stem cell niche identifies key regulators of adult neurogenesis

Neural stem cells (NSCs) generating new neurons are restricted to few niches in the adult mammalian brain, while the remainder rather promotes gliogenesis. Here we take advantage of the spatial separation of an NSC niche (the subependymal zone) and the region to where the newly generated neurons migrate and integrate (the olfactory bulb). Using state-of-the-art mass spectrometry we present a comprehensive proteomic characterization of these niches compared to a region of the normal brain parenchyma (cerebral cortex) that is not contusive to neurogenesis and new neuron integration. We find unique compositions of regulatory ECM components in the neurogenic niche, with quiescent NSCs as a main source of their local ECM, including the multi-functional enzyme transglutaminase 2 that we identify as crucial for neurogenesis. Atomic force microscopy further corroborates indications from the proteome that neurogenic niches are significantly stiffer than the non-neurogenic parenchyma, highlighting the unique properties of these special niches.