Ben W. Dulken 1 , 2 , 3 , Matthew T. Buckley 1 , Paloma Navarro Negredo 1 , Naresha Saligrama 4 , 5 , Romain Cayrol 6 , Dena S. Leeman 1 , 7 , Benson M. George 2 , 3 , Stéphane C. Boutet 8 , Katja Hebestreit 1 , John V. Pluvinage 9 , Tony Wyss-Coray 9 , Irving L. Weissman 3 , Hannes Vogel 6 , Mark M. Davis 4 , 5 , 10 , Anne Brunet 1 , 11 , 12
03 July 2019
The mammalian brain contains neurogenic niches comprising neural stem cells (NSCs) and other cell types. Neurogenic niches become less functional with age, but how they change during aging remains unclear. Here we perform single cell RNA-sequencing of young and old neurogenic niches in mice. Analysis of 14,685 single cell transcriptomes reveals a decrease in activated NSCs, changes in endothelial cells and microglia, and infiltration of T cells in old neurogenic niches. Surprisingly, T cells in old brains are clonally expanded and generally distinct from those in old blood, suggesting they may experience specific antigens. T cells from old brains express interferon γ, and the subset of NSCs with a high interferon response shows decreased proliferation in vivo. Interestingly, T cells can inhibit NSC proliferation in co-cultures and in vivo, in part by secreting interferon. Our study reveals an interaction between T cells and NSCs in old brains, opening potential avenues to counter age-related decline in brain function.