Cited by 1,155Neurogenesis and neuroplasticity mechanismsSingle-cell and spatial transcriptomicsNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index; 15 of the 23 sources its claims cite were checked for support.

Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system

Open access

Abstract

One size does not fit all: Oligodendrocytes are best known for their ability to myelinate brain neurons, thus increasing the speed of signal transmission. Marques et al. surveyed oligodendrocytes of developing mice and found unexpected heterogeneity. Transcriptional analysis identified 12 populations, ranging from precursors to mature oligodendrocytes. Transcriptional profiles diverged as the oligodendrocytes matured, building distinct populations. One population was responsive to motor learning, and another, with a different transcriptome, traveled along blood vessels. Science , this issue p. 1326

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

Single-cell RNA sequencing of 5,072 oligodendrocyte-lineage cells from ten mouse CNS regions revealed multiple transcriptionally distinct populations along a differentiation continuum, with mature subtypes varying by region. The study also identified a Pdgfra+ vascular/leptomeningeal population and an ITPR2+ oligodendrocyte population responsive to motor learning.

Key findings

  • Across 5,072 cells from ten CNS regions, clustering resolved a continuum from Pdgfra+ OPCs through committed precursors and newly formed oligodendrocytes to six mature oligodendrocyte states; the abstract describes 12 populations while the main text describes 13 distinct cell populations.
  • OPCs co-expressed Pdgfra and Cspg4, with about 10% co-expressing cell cycle genes; 16% of juvenile OPCs were cycling versus roughly 3% of adult OPCs. Committed precursors lacked Pdgfra/Cspg4 and expressed Neu4, Sox6, Bmp4, and Gpr17; newly formed oligodendrocytes expressed Tcf7l2 and Casr; myelin-forming cells expressed Mal, Mog, Plp1, Opalin, and Serinc5; mature cells expressed Klk6, Apod, Trf, and Pmp22.
  • Mature oligodendrocyte subsets were region-enriched: MOL5 was broadly present, while subsets of MOL5 and MOL6 were mainly found in adult S1 cortex and corpus callosum. Regions were classified as immature, intermediate, or mature based on juvenile cell-type distributions.
  • A second Pdgfra+ population, VLMCs, was distinct from OPCs, expressed Lum, pericyte markers Vtn and Tbx18, and basal lamina components, and localized to blood vessels and meninges. ITPR2+/SOX10+ cells increased about 50% in the corpus callosum after 2 days of complex wheel running versus non-runners; ITPR2+/SOX10+ percentages were 77±4% in CA1 and 48±7% in S1 cortex at P7, falling below 20% later, and 47±4% at P7 and 37±1% at P21 in corpus callosum, with 10–20% remaining at P90.

Methods

  • Single-cell RNA-Seq was performed on 5,072 cells expressing oligodendrocyte-lineage markers from ten regions of the mouse juvenile and adult CNS, including sorting from Pdgfra-H2B-GFP and Pdgfra-Cre-RCE mice.
  • Main analyses included biclustering, hierarchical clustering, t-SNE projection, pseudotime analysis, differential expression, and Gene Ontology enrichment; findings were validated with single-molecule fluorescence in situ hybridization, immunostaining, and lineage tracing.
  • Motor learning was assessed using the complex wheel paradigm, comparing runners and non-runners after 2 days and counting ITPR2+/SOX10+ cells in the corpus callosum.

Limitations

  • The paper does not state limitations explicitly. Evident limitations include the mouse-only juvenile/adult design, which may not translate to human development or disease, and sampling of ten CNS regions that may miss other populations.
  • Evident: most mature oligodendrocyte subtype distinctions rely on transcriptomic clustering and marker expression, with functional roles for most subsets not directly tested; the complex wheel result is correlative and based on a short 2-day paradigm.
  • Evident: the abstract and main text differ in population count (12 versus 13), and the described transcriptional continuum may make boundaries between discrete states uncertain.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1126/science.aaf6463

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

48 Own result · 12 Own interpretation · 7 Partly supported · 5 No full text of the sources · 4 Supported · 1 Mixed support · 1 Sources not found · accuracy not yet measured

Show all 54 claims

  • It may state two separate claims as one. 20
  • Probably not a substantial claim. 3
  • The quote only partly states this claim. 1
24 of 24
  • The paper relies on this without support.

    Transcriptional clusters identified by clustering analyses correspond to biologically distinct oligodendrocyte populations.

    “Biclustering analysis (6) (Fig. S1B and S15), hierarchical clustering (Fig. 1C) and differential expression analysis (Supporting File Supplementary Excel S1 and S2) led to the identification of thirteen distinct cell populations.”
  • The paper relies on this without support.

    The sampled regions and cells are representative of the mouse CNS oligodendrocyte lineage.

    “We analyzed 5072 transcriptomes of single cells expressing markers from the oligodendrocyte lineage, isolated from ten distinct regions of the anterior-posterior and dorsal-ventral axis of the mouse juvenile and adult CNS”
  • The paper relies on this without support.

    The increase in ITPR2+/SOX10+ cells after complex wheel running reflects differentiation of OPCs into ITPR2+ cells rather than other sources.

    “Thus, novel motor activity might trigger rapid differentiation of OPCs into ITPR2+ committed precursors/newly-formed oligodendrocytes that contribute to early learning by facilitating electrical transmission”
  • The paper relies on this without support.

    The classification of regions as immature, intermediate or mature based on cell type distribution reflects developmental maturation.

    “Based on the distribution of cell types in the juvenile mice, we classified regions as immature (anterior regions such as amygdala and hippocampus), intermediate (corpus callosum, zona incerta, striatum and hypothalamus) and mature (cortex and posterior regions such as dorsal horn and SN-VTA)”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Research works printed but not linked: 1

  1. Rio-Hortega P. d., Tercera aportacion al conocimiento morfologico e interpretacion funcional de la oligodendroglia. Mem. Real Soc. Esp. Hist. Nat. 14, 5–122 (1928).

Cited by

Sorted by citations

See all 1,155

Metadata

Authors
Marques, S., Zeisel, A., Codeluppi, S., van Bruggen, D., Mendanha Falcão, A., Xiao, L., Li, H., Häring, M., Hochgerner, H., Romanov, R. A., Gyllborg, D., Muñoz-Manchado, A. B., La Manno, G., Lönnerberg, P., Floriddia, E. M., Rezayee, F., Ernfors, P., Arenas, E., Hjerling-Leffler, J., Harkany, T., Richardson, W. D., Linnarsson, S., & Castelo-Branco, G.
Affiliations
  • Karolinska Institutet (SE)
  • Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.
  • Second Military Medical University (CN)
  • University College London (GB)
Corresponding author
  • Marques, Sueli
  • Zeisel, Amit
  • Linnarsson, Sten
Venue
Science
Published
2016-06-10
Volume
352
Issue
6291
Pages
1326-1329
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2415341492
Cited by
1,132
References
33
Citations by year
2026: 119 · 2025: 135 · 2024: 138 · 2023: 120 · 2022: 117 · 2021: 144 · 2020: 107 · 2019: 96 · 2018: 75 · 2017: 65 · 2016: 11
FWCI
33.95
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • RODIN (Universidad de Cádiz) (submittedVersion, cc-by-nc-nd)
Funders
  • Swedish Research Council
  • Swedish Cancer Society
  • Wallenberg Scholar
  • Söderberg Foundation
  • Linnaeus Center in Developmental Biology for Regenerative Medicine (2011-3116, 2011-3318)
  • Swedish Foundation for Strategic Research
  • European Union (EU)
  • Karolinska Institutet
  • EU FP7 (GA-2012-600394)
  • Petrus and Augusta Hedlunds Foundation
  • Novo Nordisk Foundation
  • European Research Council (ERC)
  • National Natural Science Foundation of China (31471013)
  • UK Biotechnology and Biological Sciences Research Council (BB/L003236/1)
  • Human Frontier Science Program
  • ERC (293544, 261063)
  • Wellcome Trust (100269/Z/12/Z, 108726/Z/15/Z)
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
oligodendrocyte differentiation, oligodendrocyte precursor cells, PDGFRA, single-cell transcriptomics, mouse brain development, adult brain, motor learning, transcriptional dynamics
MeSH terms
Chondroitin Sulfate Proteoglycan 4, Animals, Antigens, Brain, Cells, Cultured, Learning, Motor Activity, Myelin Sheath, Oligodendroglia, Proteoglycans, RNA, Messenger, Biomarkers, Sequence Analysis, RNA, Cell Lineage, Receptor, Platelet-Derived Growth Factor alpha, Mice, Inositol 1,4,5-Trisphosphate Receptors, Neurogenesis, Single-Cell Analysis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review