GSE137852
Ependyma-expressed CCN1 restricts the size of the neural stem cell pool in the adult ventricular-subventricular zone
Adult neural stem cells (NSCs) reside in specialized niches, which hold a balanced number of NSCs, their progeny, and other cells. How niche capacity is regulated to contain a specific number of NSCs remains unclear. Here, we show that ependyma-derived matricellular protein CCN1 (cellular communication network factor 1) negatively regulates niche capacity and NSC number in the adult ventricular-subventricular zone (V-SVZ). Adult ependyma-specific deletion of Ccn1 transiently enhanced NSC proliferation and reduced neuronal differentiation in mice, increasing the numbers of NSCs and NSC units. Although proliferation of NSCs and neurogenesis seen in Ccn1 knockout mice eventually returned to normal, the expanded NSC pool was maintained in the V-SVZ until old age. Inhibition of EGFR signaling prevented expansion of the NSC population observed in CCN1 deficient mice. Thus, ependyma-derived CCN1 restricts NSC expansion in the adult brain to maintain the proper niche capacity of the V-SVZ. Overall design: Mice received tamoxifen treatment to induce recombination, which resulted in GFP expression and Ccn1 gene deletion in the ependymal cells. 2 days after TAM treatment, ependymal cells were purified by FACS from the V-SVZ of Ctrl and Ccn1cKO mice, respectively. Gating was mannually set according to GFP expression level in the ependymal cells relative to wild-type cells. Three samples from each genotype were processed for RNA sequencing and bioinformatical analysis.