Single-cell analysis reveals T cell infiltration in old neurogenic niches

Ben W. Dulken, Matthew T. Buckley, Paloma Navarro Negredo, Naresha Saligrama, Romain Cayrol, Dena S. Leeman, Benson M. George, Stéphane C. Boutet, Katja Hebestreit, John V. Pluvinage, Tony Wyss-Coray, Irving L. Weissman, Hannes Vogel, Mark M. Davis, Anne Brunet

Research output: Contribution to journalArticlepeer-review

303 Scopus citations

Abstract

The mammalian brain contains neurogenic niches that comprise neural stem cells and other cell types. Neurogenic niches become less functional with age, but how they change during ageing remains unclear. Here we perform single-cell RNA sequencing of young and old neurogenic niches in mice. The analysis of 14,685 single-cell transcriptomes reveals a decrease in activated neural stem cells, changes in endothelial cells and microglia, and an infiltration of T cells in old neurogenic niches. T cells in old brains are clonally expanded and are generally distinct from those in old blood, which suggests that they may experience specific antigens. T cells in old brains also express interferon-γ, and the subset of neural stem cells that has a high interferon response shows decreased proliferation in vivo. We find that T cells can inhibit the proliferation of neural stem cells in co-cultures and in vivo, in part by secreting interferon-γ. Our study reveals an interaction between T cells and neural stem cells in old brains, opening potential avenues through which to counteract age-related decline in brain function.

Original languageEnglish
Pages (from-to)205-210
Number of pages6
JournalNature
Volume571
Issue number7764
DOIs
StatePublished - Jul 11 2019

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