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 and Anne Brunet ()
Additional contact information
Ben W. Dulken: Stanford University
Matthew T. Buckley: Stanford University
Paloma Navarro Negredo: Stanford University
Naresha Saligrama: Stanford University
Romain Cayrol: Stanford University School of Medicine
Dena S. Leeman: Stanford University
Benson M. George: Stanford University
Stéphane C. Boutet: Fluidigm Corporation
Katja Hebestreit: Stanford University
John V. Pluvinage: Stanford University
Tony Wyss-Coray: Stanford University School of Medicine
Irving L. Weissman: Stanford University
Hannes Vogel: Stanford University School of Medicine
Mark M. Davis: Stanford University
Anne Brunet: Stanford University

Nature, 2019, vol. 571, issue 7764, 205-210

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1362-5

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