The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Single-cell analysis reveals T cell infiltration in old neurogenic niches
Open accessAbstract
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.
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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.”
From Molecular and spatial signatures of mouse brain aging at single-cell resolution (2023) · cites this paper as [41]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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).”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [42]
Experimental — accuracy not yet measuredIn 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).”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [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.”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [49]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
In the citing paper
“Immunofluorescence staining confirmed the infiltration of T cells in the regenerative regions of aged mice and humans7,70.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
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.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [7]
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).”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as 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).”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as Dulken et al., 2019
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Citations
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Metadata
- Authors
- Dulken, B. W., Buckley, M. T., Navarro Negredo, P., Saligrama, N., Cayrol, R., Leeman, D. S., George, B. M., Boutet, S. C., Hebestreit, K., Pluvinage, J. V., Wyss-Coray, T., Weissman, I. L., Vogel, H., Davis, M. M., & Brunet, A.
- Affiliations
- Institute for Stem Cell Biology and Regenerative Medicine (US)
- Stanford University (US)
- Stanford Medicine (US)
- Genentech (US)
- 10X Genomics (United States) (US)
- Verge Genomics (United States) (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Brunet, Anne
- ORCID
- Venue
- Nature
- Published
- 2019-07-03
- Volume
- 571
- Issue
- 7764
- Pages
- 205-210
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7111535
- OpenAlex
- W2954434934
- Cited by
- 521
- References
- 64
- Citations by year
- 2026: 36 · 2025: 74 · 2024: 75 · 2023: 105 · 2022: 82 · 2021: 71 · 2020: 64 · 2019: 13
- FWCI
- 22.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Funders
- National Institute on Aging (T32AG047126, P01AG036695)
- National Human Genome Research Institute (T32HG000044)
- National Institute of General Medical Sciences (T32GM007365)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- neurogenic niche, brain aging, T cell infiltration, neural stem cells, interferon-gamma, clonal expansion, microglia, endothelial cells, single-cell transcriptomics
- MeSH terms
- Aging, Animals, Blood, Brain, Cell Movement, Clone Cells, Interferon-gamma, Male, Mice, Inbred C57BL, T-Lymphocytes, Signal Transduction, Sequence Analysis, RNA, Microglia, Coculture Techniques, Endothelial Cells, Cell Proliferation, Mice, Stem Cell Niche, Neurogenesis, Neural Stem Cells, Single-Cell Analysis, Transcriptome
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