Cited by 334Neurogenesis and neuroplasticity mechanismsSingle-cell and spatial transcriptomicsDevelopmental Biology and Gene Regulation

Single-cell transcriptomic analysis defines heterogeneity and transcriptional dynamics in the adult neural stem cell lineage

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Dulken, Ben W., Leeman, Dena S., Boutet, Stéphane C., Hebestreit, Katja, Brunet, Anne·2017·Cell Reports

Abstract

Neural stem cells (NSCs) in the adult mammalian brain serve as a reservoir for the generation of new neurons, oligodendrocytes, and astrocytes. Here, we use single-cell RNA sequencing to characterize adult NSC populations and examine the molecular identities and heterogeneity of in vivo NSC populations. We find that cells in the NSC lineage exist on a continuum through the processes of activation and differentiation. Interestingly, rare intermediate states with distinct molecular profiles can be identified and experimentally validated, and our analysis identifies putative surface markers and key intracellular regulators for these subpopulations of NSCs. Finally, using the power of single-cell profiling, we conduct a meta-analysis to compare in vivo NSCs and in vitro cultures, distinct fluorescence-activated cell sorting strategies, and different neurogenic niches. These data provide a resource for the field and contribute to an integrative understanding of the adult NSC lineage.

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Crossref · 10.1016/j.celrep.2016.12.060

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  • Overlapping TF gradients accompany cellular differentiation in systems including exit from pluripotency, organogenesis, and tissue regeneration by adult stem cells.

    “Similar overlapping TF gradients accompany cellular differentiation in systems ranging from the exit from pluripotency5 over organogenesis6 to tissue regeneration by other adult stem cells.7,8”
  • Previous low-throughput single-cell studies have begun to illuminate the stages of qNSC activation in the adult V-SVZ, focusing on NSCs purified by FACS from the lateral wall and the neuronal lineage.

    “Previous single-cell studies using low-throughput approaches have begun to illuminate the stages of qNSC activation in the adult V-SVZ (Basak et al., 2018; Dulken et al., 2017; Llorens-Bobadilla et al., 2015; Luo et al., 2015), focusing on NSCs purified by fluorescence-activated cell sorting (FACS) from the lateral wall and the neuronal lineage.”
  • GSEA revealed a clear correspondence between the neuronal lineage trajectory and previously published studies with lower throughput.

    “GSEA revealed a clear correspondence between our neuronal lineage trajectory and previously published studies with lower throughput (Figures S2B and S2C; Dulken et al., 2017; Llorens-Bobadilla et al., 2015).”
  • All profiling studies in the adult V-SVZ, including recent low-throughput single-cell studies, have focused only on the lateral wall and the neuronal lineage.

    “Although transcriptome analysis in the postnatal V-SVZ has uncovered molecular differences between the dorsal and the lateral walls (Azim et al., 2015), all profiling studies in the adult V-SVZ, including recent low-throughput, single-cell studies, have focused only on the lateral wall and the neuronal lineage (Basak et al., 2018; Codega et al., 2014; Dulken et al., 2017; Llorens-Bobadilla et al.,”
  • Top markers that correlated with both NPCs and OPCs included S100a6, Notum, Dbi, and Sfrp1, as well as known V-SVZ qNSC activation and injury-response markers, such as Ascl1, Vim, Thbs4, and Rpl32.

    “Top markers that correlated with both NPCs and OPCs included S100a6, Notum, Dbi, and Sfrp1, as well as known V-SVZ qNSC activation and injury-response markers, such as Ascl1, Vim, Thbs4, and Rpl32 (Benner et al., 2013; Dulken et al., 2017; Llorens-Bobadilla et al., 2015; Figure 5B).”

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Authors
Dulken, B. W., Leeman, D. S., Boutet, S. C., Hebestreit, K., & Brunet, A.
Affiliations
  • Institute for Stem Cell Biology and Regenerative Medicine (US)
  • Stanford Medicine (US)
  • Standard BioTools (United States) (US)
  • Stanford University (US)
Corresponding author
Brunet, Anne
Venue
Cell Reports
Publisher
Elsevier BV
Published
2017-01
Volume
18
Issue
3
Pages
777-790
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2578839378
Cited by
334
References
46
Citations by year
2026: 15 · 2025: 33 · 2024: 34 · 2023: 35 · 2022: 37 · 2021: 44 · 2020: 32 · 2019: 50 · 2018: 40 · 2017: 13 · 2016: 1
FWCI
15.61
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • NIH Training Grant (T32 GM7365)
  • Stanford MSTP program
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
adult neural stem cells, transcriptional dynamics, stem cell activation, stem cell differentiation, cell surface markers, neurogenic niche, single-cell transcriptomics
MeSH terms
Sodium-Potassium-Exchanging ATPase, Algorithms, Animals, Astrocytes, Cell Differentiation, RNA, Transcription Factors, Sequence Analysis, RNA, Connexin 43, Homeodomain Proteins, Cell Lineage, Ki-67 Antigen, Principal Component Analysis, Mice, Neurogenesis, Neural Stem Cells, Single-Cell Analysis, Transcriptome

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