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
Naturevolume 571, pages205–210 (2019) | Download Citation
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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.
Data availability
All raw sequencing reads for single-cell RNA-seq data (10x Genomics, Smart-seq v4, and Fluidigm C1) as well as bulk RNA-seq data can be found under BioProject PRJNA450425. The command and configuration files, in addition to a list of all versioned dependencies present in the running environment, are available in the Github repository for this paper (https://github.com/gitbuckley/SingleCellAgingSVZ).
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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