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 accessAbstract
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.
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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
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“COL1A1-/PDGFRA+ OPCs were distributed in the parenchyma, in close association but not overlapping with the vasculature”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Partly supportedcites [18] Tsai HH Oligodendrocyte precursors migrate along vasculature in the developing nervous system Science 2016 351 379 384 26798014 PMC5472053 sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“consistent with a cell division turnover of 19 days in the juvenile cortex (7).”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Supportedcites [7] Young KM Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling Neuron 2013 77 873 885 23473318 PMC3842597 source
The Results section (‘OP Cell-Cycle Duration Depends on Brain Region and Declines with Age’) reports an OP cell-cycle time of approximately 19 days in the motor cortex of P21 mice. This supports the cited juvenile-cortex cell-division timescale; the paper presents it as an approximate cell-cycle time, not an exact value. (LLM, conf=0.94)
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“a process that requires active myelination (20).”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Supportedcites [20] McKenzie IA Motor skill learning requires active central myelination Science 2014 346 318 322 25324381 PMC6324726 source
The Abstract reports that blocking production of new oligodendrocytes prevented mice from mastering the complex wheel, and states that active myelination during adulthood is required for motor skill learning. This supports the claim as a statement about learning the complex-wheel task. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“suggesting that oligodendrocyte lineage cells contribute to learning already within the first 2 days.”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Supportedcites [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), mice unable to produce new oligodendrocytes had lower daily running speeds than controls throughout the first week, including its first two days. The paper interprets this as evidence that newly formed oligodendrocytes contribute to motor-skill acquisition in mice. (LLM, conf=0.86)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Non-proliferative Nkx2.2+ precursors with a profile consistent with these cells (Fig. S10) have been observed in lesions of multiple sclerosis patients (26).”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“exhibited close to 100% overlap with SOX10 positive cells”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These tissues still maintained 10-20% ITPR2+ cells at adult stages (P90”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While Gpr17 expression decreased in these cells”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A second Pdgfra+ population, distinct from OPCs, was found along vessels.”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Twelve populations were identified, representing a continuum from Pdgfra+ oligodendrocyte precursors (OPCs) to distinct mature oligodendrocytes.”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 20
- Probably not a substantial claim. 3
- The quote only partly states this claim. 1
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“Newly-formed oligodendrocytes (NFOL1-2) expressed genes induced at early stages of differentiation (12–14) (Tcf7l2, Casr”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Could not verifycites [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 sourceExperimental — accuracy not yet measured
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)
- Disputedcites [13] Swiss VA Identification of a gene regulatory network necessary for the initiation of oligodendrocyte differentiation PLoS One 2011 6 e18088 21490970 PMC3072388 sourceExperimental — accuracy not yet measured
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.
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Mature oligodendrocytes (MOL1-6) expressed late oligodendrocyte differentiation genes (12) (Klk6, Apod) and genes present in myelinating cells (Trf and Pmp22)”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Tcf7l2, involved in oligodendrocyte differentiation (15)”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Supportedcites [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
The Results section ('TCF7L2 is critical for oligodendrocyte differentiation') reports that TCF7L2-null embryos lacked expression of mature oligodendrocyte markers and concludes that TCF7L2 is required for differentiation or maturation. The Discussion likewise describes TCF7L2 as critical for oligodendrocyte differentiation. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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)”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Also stated in: § Abstract · hedged
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“expressed Neu4 and genes involved in keeping oligodendrocytes undifferentiated (Sox6, Bmp4 and Gpr17) (9–11)”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Not checked — no full text of the sourcecites [9] Stolt CC SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function Dev Cell 2006 11 697 709 17084361 source
- Partly supportedcites [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 sourceExperimental — accuracy not yet measured
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)
- Supportedcites [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
The Results section, “Identification of oligodendrocyte lineage-specific GPR17” (page unavailable), reports GPR17 expression in oligodendrocyte-lineage cells, including cells expressing the precursor marker Pdgfrα. The Discussion section, “GPR17 as a negative regulator of CNS myelination” (page unavailable), concludes that GPR17 negatively regulates oligodendrocyte differentiation. This supports the Gpr17 portion attributed to this source among citations 9–11. (LLM, conf=0.88)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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)”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Partly supportedcites [20] McKenzie IA Motor skill learning requires active central myelination Science 2014 346 318 322 25324381 PMC6324726 sourceExperimental — accuracy not yet measured
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)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“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).”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Partly supportedcites [20] McKenzie IA Motor skill learning requires active central myelination Science 2014 346 318 322 25324381 PMC6324726 sourceExperimental — accuracy not yet measured
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)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Differentiation-committed oligodendrocyte precursors were enriched in cell fate commitment and adhesion genes”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Differentiation-committed oligodendrocyte precursors (COPs) were distinct from OPCs (lacking Pdgfra and Cspg4)”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We identified a second Pdgfra+ population, vascular and leptomeningeal cells (VLMCs), distinct from OPCs and segregated from all oligodendrocyte lineage cells”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Potassium channels and TRPs were also expressed in a cell type-specific manner, displaying a scattered distribution within populations”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While some populations, such as MOL5, were present throughout the regions, other MOLs where enriched in certain regions”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These populations were also observed in the adult corpus callosum and S1 cortex, albeit in considerably lower numbers compared to juvenile mice”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although most glutamate receptor subunits were expressed throughout oligodendrocyte lineage cells, there was preferential expression in some populations”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We confirmed the presence of GRM3 in the oligodendrocyte lineage (Pdgfra-Cre-RCE) and specifically in CC1+ mature oligodendrocytes in the juvenile cortex”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mature oligodendrocyte subtype specification occurred later at postnatal stages and in a region specific manner.”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“these cells were originally described as morphologically heterogeneous (2).”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Not matchedcites [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.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Not checked — no full text of the sourcecites [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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Optic nerve oligodendrocytes can form axon-myelinic synapses, responding to axonal action potentials via glutamate ionotropic NMDA receptors (24).”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
What the sources say
- Not checked — no full text of the sourcecites [24] Micu I The molecular physiology of the axo-myelinic synapse Exp Neurol 2016 276 41 50 26515690 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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”
§ Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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)”
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?
The cited source says what the claim attributes to it.
In the citing paper
“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
The cited source says what the claim attributes to it.
In the citing paper
“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
The cited source says what the claim attributes to it.
In the citing paper
“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
The cited source says what the claim attributes to it.
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“The algorithm has by now been extensively validated using both computational (including comparisons to PCA, and independent-component analysis, tSNE, and GP-LVM) biological validation tools 9, 63–66.”
From Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes (2017) · cites this paper as [66]
In the citing paper
“sc/snRNA-seq also provides insight into the diversity of glial cells including the oligodendrocyte lineage (Marques et al., 2016) and functional states of microglia (Masuda et al., 2019).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Marques et al., 2016
In the citing paper
“Differentiation trajectories of newborn neurons and oligodendrocytes in adults can also be reconstructed (Habib et al., 2016; Marques et al., 2016).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Marques et al., 2016
In the citing paper
“Continuous trajectories occur during brain development (Nowakowski et al., 2017) and in differentiating cell populations in the adult, such as oligodendrocyte lineage cells (Marques et al., 2016) or newborn granule cells in the dentate gyrus of the hippocampus (Habib et al., 2016).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Marques et al., 2016
In the citing paper
“such as Ptprz1, a marker of oligodendrocyte precursor cells38,39”
From Spatial epigenome–transcriptome co-profiling of mammalian tissues (2023) · cites this paper as [38]
In the citing paper
“These previously uncharacterized temporal modules comprised oligodendrocyte lineage progression TFs (e.g., Kcnip3, Olig2, Sox2, and Klf9; Maki et al., 2013; Marques et al., 2016; Tokumoto et al., 2017; Wu et al., 2012) and co-expression partners (e.g., Hes5, Eno1, Sox21, Purb, Zfp275, Foxj2, Zeb2, Tsc22d3, and Hopx; Figure 4F).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Marques et al., 2016
In the citing paper
“We next generated a force-directed visualization of the oligodendrocyte lineage k-nearest neighbors graph to define their lineage order (Figure 4A), which recapitulated the predicted lineage order previously reported from single cell RNA (scRNA)-seq profiles of oligodendrocyte differentiation (Marques et al., 2016; Figure S2E).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Marques et al., 2016
In the citing paper
“It appears that aging-driven down-regulation of ribosomal genes had been widely accepted, mostly based on transcriptomic studies in yeast 56,57 .”
From Single-cell transcriptomic profiling of the aging mouse brain (2019) · cites this paper as [57]
Citations
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
(2008) · Journal of Machine Learning Research · Cited by 33,051
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108
Trapnell, C., Cacchiarelli, D., Grimsby, J., Pokharel, P., Li, S., Morse, M., Lennon, N. J., Livak, K. J., Mikkelsen, T. S., & Rinn, J. L. (2014) · Nature Biotechnology · doi:10.1038/nbt.2859 · Cited by 7,314 · cited 1×
“Applying the unsupervised algorithm Monocle (18) confirmed the ordering of cell types (Fig.”
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · cited 2×
“Newly-formed oligodendrocytes (NFOL) 1 and 2 expressed genes induced at early stages of differentiation (13-15) (Tcf7l2, Mpzl1 and Casr, Fig.”
Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Zeisel, A., Muñoz-Manchado, A. B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. (2015) · Science · doi:10.1126/science.aaa1934 · Cited by 3,124
Self-citationKessaris, N., Fogarty, M., Iannarelli, P., Grist, M., Wegner, M., & Richardson, W. D. (2006) · Nature Neuroscience · doi:10.1038/nn1620 · Cited by 1,195 · cited 1×
“A largely homogeneous population is thought to execute these functions throughout the CNS (1).”
Motor skill learning requires active central myelination
McKenzie, I. A., Ohayon, D., Li, H., Paes de Faria, J., Emery, B., Tohyama, K., & Richardson, W. D. (2014) · Science · doi:10.1126/science.1254960 · Cited by 1,177 · cited 3×
“In this paradigm, 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 (25).”
InfluentialSelf-citationOligodendrocyte Dynamics in the Healthy Adult CNS: Evidence for Myelin Remodeling
Young, K. M., Psachoulia, K., Tripathi, R. B., Dunn, S.-J., Cossell, L., Attwell, D., Tohyama, K., & Richardson, W. D. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.006 · Cited by 919
Self-citation
Research works printed but not linked: 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
Scenic: single-cell regulatory network inference and clustering.
Aibar, S., González-Blas, C. B., Moerman, T., Huynh-Thu, V. A., Imrichova, H., Hulselmans, G., Rambow, F., Marine, J.-C., Geurts, P., Aerts, J., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4463 · Cited by 6,520
“Note that this cancer trajectory represents a different “trajectory” compared to normal oligodendrocyte differentiation (Figure S14 for the SCENIC analysis of 5069 oligodendrocytes 58 ).”
BackgroundMolecular Architecture of the Mouse Nervous System
Zeisel, A., Hochgerner, H., Lönnerberg, P., Johnsson, A., Memic, F., van der Zwan, J., Häring, M., Braun, E., Borm, L. E., La Manno, G., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.021 · Cited by 2,552
Self-citationA molecular atlas of cell types and zonation in the brain vasculature
Vanlandewijck, M., He, L., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., Nahar, K., Lebouvier, T., Laviña, B., Gouveia, L., et al. (2018) · Nature · doi:10.1038/nature25739 · Cited by 1,892
Shared and distinct transcriptomic cell types across neocortical areas
Tasic, B., Yao, Z., Graybuck, L. T., Smith, K. A., Nguyen, T. N., Bertagnolli, D., Goldy, J., Garren, E., Economo, M. N., Viswanathan, S., et al. (2018) · Nature · doi:10.1038/s41586-018-0654-5 · Cited by 1,746
Molecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,531
“The first stage of analysis robustly grouped cells into 8–11 broad classes (Data S2), including neurons, astrocytes, microglia/macrophages, oligodendrocytes, polydendrocytes (oligodendrocyte progenitor cells), and components of the vasculature—endothelial cells, fibroblast-like cells, andmural cells (Abbott et al., 20…”
Background
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
- ORCID
- Venue
- Science
- Published
- 2016-06-10
- Volume
- 352
- Issue
- 6291
- Pages
- 1326-1329
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5221728
- 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
- green
- www.ncbi.nlm.nih.gov
- 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
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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.
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