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

In the citing paper

“we also observed a substantial increase in the abundance of T cells in old animals (Figure 2A), although the change did not reach statistical significance due to the small number of cells detected in this rare cell population.”

In the citing paper

“Among the genes that were most differentially expressed in oligodendrocytes were several genes that characterize this cell type during ageing and neurodegeneration, including H2-D1, Ifi27, C4b, Spock3, Trf or Sgk1 (refs. 42,43).”

In the citing paper

“Interestingly, activated NSCs exhibit fewer overall transcriptomic changes with ageing than quiescent NSCs6–9,63,64, perhaps because activated NSCs are recently generated and do not have the time to accumulate damage, or because they ‘dilute’ the damage as they proliferate.”

In the citing paper

“Indeed, increased clonal expansion and CD8+ T cell infiltration in the brain are observed both in AD patients and during aging (48, 49).”

In the citing paper

“Once activated CD8+ T cells have infiltrated the brain, they can release IFN-γ to stimulate excessive microglial synaptic pruning or inhibit adult neural stem cell proliferation (44, 49), impairing neuronal homeostasis.”

In the citing paper

“In the brain, old age is accompanied by an increase in the number of quiescent NSCs and a decrease in their ability to activate6–8.”

In the citing paper

“For example, in the mouse brain, single-cell RNA-seq analyses indicate that the number of activated neural stem cells (NSCs) and neuroblasts (progeny) decreases with ageing in both the subventricular zone (SVZ) NSC niche and the hippocampal NSC niche6–9 — the main locations of NSCs.”

In the citing paper

“Indeed, single-cell RNA-seq indicated that ageing is accompanied by infiltration of clonally expanded cytotoxic CD8+ T cells in old neurogenic niches7.”

In the citing paper

“For example, in the SVZ neurogenic niche, RNA-seq studies uncovered the presence of 11 cell types, including endothelial cells, microglia, oligodendrocytes and pericytes7.”

In the citing paper

“For example, owing to the infiltration of immune cells, the activation of macrophages and microglia, and the presence of senescent cells, the NSC niche milieu likely becomes extremely inflammatory during ageing6–8.”

In the citing paper

“Immunofluorescence staining confirmed the infiltration of T cells in the regenerative regions of aged mice and humans7,70.”

In the citing paper

“Ageing is accompanied by strong transcriptional changes in niche cells such as endothelial cells (which form blood vessels) and microglia (the immune cells of the brain), consistent with inflammation7.”

In the citing paper

“inflammatory cytokines, including interferon, and inflammatory cytokines (interleukin-33 (IL-33) and CXCL10), are upregulated during ageing in the NSC niche7,8.”

In the citing paper

“In the brain SVZ neurogenic region, T cells can secrete interferon-γ (IFNγ), and IFNγ signalling is increased in the entire neurogenic region. NSCs respond to IFNγ by decreased proliferation, which is restored (at least in vitro) by blocking antibodies to IFNγ7.”

In the citing paper

“These aNSCs are enriched in neurogenic areas at young age and their number declines in old individuals (Dulken et al., 2019).”

In the citing paper

“We validated our findings in an independent dataset, using publicly available scRNA-seq data from dissected SVZ of young and old male mice (Dulken et al., 2019) (Figure S8A). Though generated using a different cohort, region and method, the CAS increase was most pronounced in microglia which is consistent with our data (Figure S8B-G).”