Cited by 259Neurogenesis and neuroplasticity mechanismsSingle-cell and spatial transcriptomicsNeuroinflammation and Neurodegeneration Mechanisms

A Single-Cell RNA Sequencing Study Reveals Cellular and Molecular Dynamics of the Hippocampal Neurogenic Niche

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Artegiani, Benedetta, Lyubimova, Anna, Muraro, Mauro, van Es, Johan H., van Oudenaarden, Alexander, Clevers, Hans·2017·Cell Reports

Abstract

Adult neurogenesis in the murine dentate gyrus occurs in a specialized microenvironment that sustains the generation of neurons during life. To fully understand adult neurogenesis, it is essential to determine the neural stem cell (NSC) and progenitor developmental stages, their molecular determinants, and the niche cellular and molecular composition. We report on a single-cell RNA sequencing study of the hippocampal niche, performed by isolating all the non-neuronal cell populations. Our analysis provides a comprehensive description of the dentate gyrus cells, and it allows the identification of exclusive cell-type-specific markers. We define the developmental stages and transcriptional dynamics of NSCs and progenitors, and we find that, while NSCs represent a heterogeneous cellular continuum, progenitors can be grouped into distinct subtypes. We determine the oligodendrocyte lineage and transcriptional dynamics, and we describe the microglia transcriptional profile and activation state. The combined data constitute a valuable resource to understand regulatory mechanisms of adult neurogenesis.

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Crossref · 10.1016/j.celrep.2017.11.050

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  • In the mouse brain, single-cell RNA-seq analyses indicate that the number of activated neural stem cells (NSCs) and neuroblasts decreases with ageing in both the subventricular zone (SVZ) NSC niche and the hippocampal NSC niche.

    “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 brain, old age is accompanied by an increase in the number of quiescent NSCs and a decrease in their ability to activate.

    “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.”
  • 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 ageing.

    “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.”
  • Activated NSCs exhibit fewer overall transcriptomic changes with ageing than quiescent NSCs.

    “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.”

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Authors
Artegiani, B., Lyubimova, A., Muraro, M., van Es, J. H., van Oudenaarden, A., & Clevers, H.
Affiliations
Royal Netherlands Academy of Arts and Sciences (NL)
Corresponding author
Clevers, Hans
Venue
Cell Reports
Publisher
Elsevier BV
Published
2017-12
Volume
21
Issue
11
Pages
3271-3284
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2773573309
Cited by
259
References
57
Citations by year
2026: 15 · 2025: 34 · 2024: 28 · 2023: 35 · 2022: 38 · 2021: 28 · 2020: 34 · 2019: 27 · 2018: 20
FWCI
9.38
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • FEBS
  • Veni (NWO/VENI 863.15.015)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
adult neurogenesis, dentate gyrus, neural stem cells, neural progenitor cells, progenitor heterogeneity, cell type-specific markers, transcriptional dynamics, oligodendrocyte lineage, microglial activation, non-neuronal cells, single-cell transcriptomics
MeSH terms
Animals, Cell Differentiation, Female, Hippocampus, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Neurons, Oligodendroglia, RNA, Messenger, Transcription, Genetic, Biomarkers, Sequence Analysis, RNA, Microglia, Dentate Gyrus, Cell Lineage, Mice, Neurogenesis, Molecular Dynamics Simulation, Neural Stem Cells, Single-Cell Analysis

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