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Cited by 1,246Neurogenesis and neuroplasticity mechanismsSingle-cell and spatial transcriptomicsNeuroinflammation and Neurodegeneration Mechanisms

Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system

Open access
Marques, Sueli, Zeisel, Amit, Codeluppi, Simone, van Bruggen, David, Mendanha Falcão, Ana, Xiao, Lin, Li, Huiliang, Häring, Martin +15 more·2016·Science
DOI 10.1126/science.aaf6463PMC PMC5221728
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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

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.

Claims the paper makes

15 of 23 cited sources checked · 5 supported · 1 flagged · accuracy not yet measured

  • Findingcitation

    COL1A1-/PDGFRA+ OPCs are distributed in the parenchyma, in close association but not overlapping with the vasculature.

    “COL1A1-/PDGFRA+ OPCs were distributed in the parenchyma, in close association but not overlapping with the vasculature”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [18] Tsai HH Oligodendrocyte precursors migrate along vasculature in the developing nervous system Science 2016 351 379 384 26798014 PMC5472053 source

      The paper reports that PDGFRα+ OPCs associate closely with vessels during migration and describes their dispersal into CNS parenchyma (Abstract; page not provided). It does not identify the OPCs as COL1A1− or establish that they do not overlap with the vasculature; many are described as having cell bodies directly on vessel walls. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Premisecitation

    OPC cell division turnover in the juvenile cortex is 19 days.

    “consistent with a cell division turnover of 19 days in the juvenile cortex (7).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] Young KM Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling Neuron 2013 77 873 885 23473318 PMC3842597 source
  • Premisecitation

    The complex wheel paradigm requires active myelination.

    “a process that requires active myelination (20).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [20] McKenzie IA Motor skill learning requires active central myelination Science 2014 346 318 322 25324381 PMC6324726 source
  • Interpretationcitation

    Oligodendrocyte lineage cells contribute to learning already within the first 2 days.

    “suggesting that oligodendrocyte lineage cells contribute to learning already within the first 2 days.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [20] McKenzie IA Motor skill learning requires active central myelination Science 2014 346 318 322 25324381 PMC6324726 source
  • Premisecitation

    Non-proliferative Nkx2.2+ precursors with a profile consistent with these cells have been observed in lesions of multiple sclerosis patients.

    “Non-proliferative Nkx2.2+ precursors with a profile consistent with these cells (Fig. S10) have been observed in lesions of multiple sclerosis patients (26).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [26] Kuhlmann T Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis Brain 2008 131 1749 1758 18515322 source

      The Discussion identifies strongly Nkx2.2-positive cells as progenitors in adult human CNS. The ‘In early multiple sclerosis lesions’ section reports Olig2-positive progenitors in lesions and finds that only rare Olig2-positive cells co-express the proliferation marker Ki67. The lesion and proliferation analyses focused on Olig2, however, so they do not directly establish that the non-proliferative cells observed in lesions were Nkx2.2-positive. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • May combine two claims. 20
  • Classified as probably not a substantial claim. 3
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    NFOL1-2 express Tcf7l2 and Casr.

    “Newly-formed oligodendrocytes (NFOL1-2) expressed genes induced at early stages of differentiation (12–14) (Tcf7l2, Casr”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [12] Cahoy JD A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function J Neurosci 2008 28 264 278 18171944 PMC6671143 source

      The ‘Gene expression changes during astrocyte and oligodendrocyte development’ section discusses differentiation from OPCs to oligodendrocytes, but the passages found do not identify an NFOL1–2 population or report Tcf7l2 and Casr expression in it. Searches for both gene names and early oligodendrocyte differentiation found no passage establishing the attributed claim. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
    • cites [13] Swiss VA Identification of a gene regulatory network necessary for the initiation of oligodendrocyte differentiation PLoS One 2011 6 e18088 21490970 PMC3072388 source

      The Discussion (page unavailable) says Tcf7l2 must be down-regulated during early oligodendrocyte differentiation, contrary to the citing sentence’s description of it as induced at that stage. Our copy does not address Casr or expression in the NFOL1–2 subgroups. (LLM, conf=0.82)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [14] Zhang Y An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex J Neurosci 2014 34 11929 11947 25186741 PMC4152602 source

      The Additional information (Table 2; page unavailable) lists Casr among cell-type-enriched receptors, and the paper profiles newly formed oligodendrocytes (NFOs). The passages do not establish that Casr is expressed specifically by NFOL1-2, and a search for Tcf7l2 found no supporting passage. The paper uses NFO rather than the NFOL1-2 classification. (LLM, conf=0.72)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    MOL1-6 express Klk6, Apod, Trf, Pmp22.

    “Mature oligodendrocytes (MOL1-6) expressed late oligodendrocyte differentiation genes (12) (Klk6, Apod) and genes present in myelinating cells (Trf and Pmp22)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [12] Cahoy JD A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function J Neurosci 2008 28 264 278 18171944 PMC6671143 source

      The Additional information gene list includes Apod and Trf, and the Analysis of genes expressed by oligodendrocytes section identifies Trf as an established oligodendrocyte gene (pages unavailable). Our copy does not identify MOL1–6 or establish their expression of Klk6 and Pmp22, so it supports only part of the attributed claim. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Tcf7l2 is involved in oligodendrocyte differentiation.

    “Tcf7l2, involved in oligodendrocyte differentiation (15)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [15] Ye F HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction Nat Neurosci 2009 12 829 838 19503085 PMC2701973 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Oligodendrocytes have been considered a functionally homogeneous population in the CNS.

    “Oligodendrocytes have been considered as a functionally homogenous population in the central nervous system (CNS).”
    • Also stated in: § Abstract · hedged
      “While a largely homogeneous oligodendrocyte population is thought to execute these functions throughout the CNS (1)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Kessaris N Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage Nat Neurosci 2006 9 173 179 16388308 PMC6328015 source

      The Introduction reports no evidence of functional heterogeneity among oligodendrocyte lineages in the forebrain, and the Discussion describes those populations as functionally equivalent. The claim extends that finding to oligodendrocytes throughout the CNS; the paper also notes that subtle functional differences remain possible. The supplied passages have section labels but no page numbers. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    COPs express Neu4 and genes involved in keeping oligodendrocytes undifferentiated (Sox6, Bmp4, Gpr17).

    “expressed Neu4 and genes involved in keeping oligodendrocytes undifferentiated (Sox6, Bmp4 and Gpr17) (9–11)”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [9] Stolt CC SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function Dev Cell 2006 11 697 709 17084361 source
    • cites [10] Samanta J Kessler JA Interactions between ID and OLIG proteins mediate the inhibitory effects of BMP4 on oligodendroglial differentiation Development 2004 131 4131 4142 15280210 source

      The BMP4-inhibition results (Fig. 1; page unavailable in our copy) show that BMP4 treatment reduced oligodendrocyte-lineage cells, supporting BMP4’s inhibitory role. The paper does not establish that COPs express Neu4, Sox6, BMP4, or Gpr17, or address the roles of the other listed genes. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [11] Chen Y The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination Nat Neurosci 2009 12 1398 1406 19838178 PMC2783566 source

  • May combine two claims.

    Premisecitation

    Increased motor skills were apparent after 2 days in wild type mice, but not in mutant mice unable to synthesize new myelin.

    “increased motor skills were already apparent after 2 days in wild type mice, but not in mutant mice that were unable to synthesize new myelin (20)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [20] McKenzie IA Motor skill learning requires active central myelination Science 2014 346 318 322 25324381 PMC6324726 source

      In “Active myelination is required for motor skill learning” (page unavailable), the paper reports that Myrf-mutant mice performed worse than their control littermates on the complex wheel. It does not establish the claimed two-day milestone, and it says both groups improved during the first week—not that the mutants showed no improvement. The controls were Myrf(+/−) littermates, rather than wild-type mice. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    In the complex wheel paradigm, running leads to an increase in proliferating OPCs after 4 days, followed by an increase in oligodendrocytes after 8 days.

    “running on the wheel leads to an increase in the number of proliferating OPCs after 4 days, followed by an increase in oligodendrocytes after 8 days (20).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [20] McKenzie IA Motor skill learning requires active central myelination Science 2014 346 318 322 25324381 PMC6324726 source

      In “Running stimulates OP proliferation and OL production” (page unavailable), the paper reports an increased fraction of EdU-labeled OPCs after 4 days on the complex wheel, consistent with increased proliferation. It reports an increase in the absolute number of OPCs at 6 days and in oligodendrocyte-lineage cells at 11 days, not an increase in oligodendrocytes at 8 days. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    77±4% and 48±7% of SOX10+ oligodendrocytes were ITPR2+ at P7 in CA1 hippocampus and S1 cortex, respectively, and decreased to less than 20% thereafter.

    “77±4% and 48±7% of SOX10+ oligodendrocytes were ITPR2+ at P7 in the CA1 hippocampus and S1 cortex, respectively, and decreased to less than 20% thereafter”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    COPs are enriched in cell fate commitment and adhesion genes.

    “Differentiation-committed oligodendrocyte precursors were enriched in cell fate commitment and adhesion genes”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    COPs are distinct from OPCs, lacking Pdgfra and Cspg4.

    “Differentiation-committed oligodendrocyte precursors (COPs) were distinct from OPCs (lacking Pdgfra and Cspg4)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At P21, 22±2% of OPC-derived Pdgfra-H2B-GFP+ cells in S1 cortex, 25±1.5% in CA1 hippocampus, and 43±3.7% in corpus callosum were ITPR2+.

    “22±2% and 25±1.5% of the OPC-derived Pdgfra-H2B-GFP+ cells were ITPR2+ in the somatosensory (S1) cortex and CA1 hippocampus at P21 respectively, while 43±3.7% double positive cells were found in the corpus callosum”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    VLMCs are a second Pdgfra+ population distinct from OPCs and segregated from all oligodendrocyte lineage cells.

    “We identified a second Pdgfra+ population, vascular and leptomeningeal cells (VLMCs), distinct from OPCs and segregated from all oligodendrocyte lineage cells”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    16% of juvenile OPCs were in the cell cycle, compared to ~3% of adult OPCs.

    “16% of the juvenile OPCs were in the cell cycle (as determined by the simultaneous expression of more than 2 cell cycle markers, Fig. S2F), compared to ~3% of the adult OPCs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Potassium channels and TRPs were expressed in a cell type-specific manner, displaying a scattered distribution within populations.

    “Potassium channels and TRPs were also expressed in a cell type-specific manner, displaying a scattered distribution within populations”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Some populations, such as MOL5, were present throughout the regions, while other MOLs were enriched in certain regions.

    “While some populations, such as MOL5, were present throughout the regions, other MOLs where enriched in certain regions”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    COPs and NFOLs were observed in adult corpus callosum and S1 cortex, albeit in considerably lower numbers compared to juvenile mice.

    “These populations were also observed in the adult corpus callosum and S1 cortex, albeit in considerably lower numbers compared to juvenile mice”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Most glutamate receptor subunits were expressed throughout oligodendrocyte lineage cells, but there was preferential expression in some populations.

    “Although most glutamate receptor subunits were expressed throughout oligodendrocyte lineage cells, there was preferential expression in some populations”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    GRM3 is present in the oligodendrocyte lineage and specifically in CC1+ mature oligodendrocytes in the juvenile cortex.

    “We confirmed the presence of GRM3 in the oligodendrocyte lineage (Pdgfra-Cre-RCE) and specifically in CC1+ mature oligodendrocytes in the juvenile cortex”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Mature oligodendrocyte subtype specification occurred later at postnatal stages and in a region-specific manner.

    “mature oligodendrocyte subtype specification occurred later at postnatal stages and in a region specific manner.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oligodendrocytes were originally described as morphologically heterogeneous.

    “these cells were originally described as morphologically heterogeneous (2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Rio-Hortega Pd Tercera aportacion al conocimiento morfologico e interpretacion funcional de la oligodendroglia Mem Real Soc Espan Hist Nat 1928 14 40 122

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    Final maturation of oligodendrocytes might already be achieved in juvenile mice in certain regions, such as dorsal horn, but only in adulthood in others, such as corpus callosum.

    “final maturation of oligodendrocyte might already be achieved in the juvenile mice in certain regions, such as the dorsal horn, but only in adulthood in others, such as the corpus callosum.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the rat, myelination first starts in posterior regions (dorsal horn) around P7, while in anterior regions of the CNS (amygdala, hippocampus, striatum and cortex) it occurs between P21 and P28.

    “myelination first starts in the rat in posterior regions (dorsal horn) around P7, while in anterior regions of the CNS (amygdala, hippocampus, striatum and cortex) it occurs between P21 and P28 (23).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Coffey JC McDermott KW The regional distribution of myelin oligodendrocyte glycoprotein (MOG) in the developing rat CNS: an in vivo immunohistochemical study J Neurocytol 1997 26 149 161 9192283 source

  • May combine two claims.

    Premisecitation

    Optic nerve oligodendrocytes can form axon-myelinic synapses, responding to axonal action potentials via glutamate ionotropic NMDA receptors.

    “Optic nerve oligodendrocytes can form axon-myelinic synapses, responding to axonal action potentials via glutamate ionotropic NMDA receptors (24).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Micu I The molecular physiology of the axo-myelinic synapse Exp Neurol 2016 276 41 50 26515690 source

  • May combine two claims.

    Interpretationown data

    There is a transcriptional continuum between oligodendrocyte populations, with a subset representing distinct but connected stages in the maturation path from an OPC to mature oligodendrocytes.

    “indicates a transcriptional continuum between oligodendrocyte populations, with a subset representing distinct but nevertheless connected stages in the maturation path from an OPC to mature oligodendrocytes”
    Quote in the paperSubstantial claim
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?

  • Although the oligodendrocyte lineage clusters aligned well with those previously published, there was not a perfect correspondence, and subtype labels in this paper do not correspond exactly to those previously described.

    “Note that although the oligodendrocyte lineage clusters aligned well with those previously published (Figure S1H; Marques et al., 2016), there was not a perfect correspondence, and subtype labels in this paper do not correspond exactly to those previously described.”

    From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Marques et al., 2016

  • Brain fibroblast-like cells are likely identical to the vascular leptomeningeal cells (VLMCs) previously described in the mouse CNS.

    “Brain fibroblast-like cells are likely identical to the vascular leptomeningeal cells (VLMCs) that we previously described in the mouse CNS (Marques et al., 2016).”

    From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Marques et al., 2016

  • Oligodendrocytes wrap myelin sheets around axons to support long-range neurotransmission and were previously analyzed by scRNA-seq.

    “Oligodendrocytes wrap myelin sheets around axons to support long-range neurotransmission and were previously analyzed by scRNA-seq (Marques et al., 2016).”

    From Molecular Architecture of the Mouse Nervous System (2018) · cites this paper as Marques et al., 2016

  • Oligodendrocytes may modulate axon myelination in response to synaptic input, given their expression of glutamate receptor genes in mice and of excitatory synaptic proteins in zebrafish.

    “Oligodendrocytes may modulate axon myelination in response to synaptic input, given their expression of glutamate receptor genes in mice 63 and of excitatory synaptic proteins in zebrafish. 64”

    From Unique transcriptomic alterations in 5XFAD;PS19 mouse model identify glial lipid dysregulation and coordinated microglial–oligodendrocyte responses (2026) · cites this paper as [63]

  • Along the oligodendroglial lineage, myelinated mature oligodendrocytes exhibit enriched expression of MAG, MOBP, and OPALIN.

    “Along the oligodendroglial lineage, myelinated mature oligodendrocytes exhibit enriched expression of MAG, MOBP, and OPALIN (21).”

    From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [21]

Cites

Flagged first, then by citations

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

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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
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2016-06-10
Volume
352
Issue
6291
Pages
1326-1329
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aaf6463
PMC
PMC5221728
OpenAlex
W2415341492
Cited by
1,246
References
33
Citations by year
2026: 94 · 2025: 132 · 2024: 147 · 2023: 126 · 2022: 131 · 2021: 146 · 2020: 113 · 2019: 100 · 2018: 79 · 2017: 64 · 2016: 8 · 2013: 1 · 2012: 1
FWCI
40.79
Type
journal article
Language
en
Open access
Licence
www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 365 d)
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
  • 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

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