Cited by 249Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsMesenchymal stem cell research

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index; 7 of the 8 sources its claims cite were checked for support.

BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions

Open access

Abstract

BCAS1 expression identifies newly formed and actively myelinating oligodendrocytes in development, adulthood, and disease.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

BCAS1 marks a transient population of newly formed, early myelinating oligodendrocytes in mouse and human brain that is distinct from oligodendrocyte progenitor cells and mature oligodendrocytes. BCAS1+ cells are abundant during developmental myelination, persist in adult gray matter, and are reformed in a proportion of chronic multiple sclerosis lesions, including inactive lesions.

Key findings

  • BCAS1+ cells are oligodendroglial but segregate from known stages: in mouse, 16.5 ± 2.8% overlapped with NG2+ OPCs, 76.2 ± 3.5% with CC1, and 47.5 ± 3.2% with MAG; in human newborn tissue, only 3.5 ± 1.4% overlapped with NG2, 0.6 ± 0.3% with TPPP/p25, and 0% with CC1.
  • BCAS1+ cells are transient in mouse corpus callosum: after 10 days of EdU labeling, 65 ± 2.7% of BCAS1+ cells incorporated EdU, but only 7.7 ± 1.3% remained after a 40-day chase; in somatosensory cortex, EdU+/BCAS1+ cells were 12.1 ± 1.5% at +0 days and 17.9 ± 1.1% at +40 days.
  • Human white matter BCAS1+ density peaked in newborns at 154.7 ± 20.8 cells/mm², fell to 16.8 ± 4.5 cells/mm² at 2–8 years and 6.8 ± 2.3 cells/mm² at 18–26 years; frontal cortex BCAS1+ density remained 30–90 cells/mm² throughout adult life.
  • In mouse somatosensory cortex, BCAS1+ myelinating oligodendrocyte density was 715.5 ± 66.8 cells/mm³ at P40, 379 ± 11.9 at 4 months, 347.7 ± 26.6 at 7 months, and 71.2 ± 11.7 at 21 months; SILAC showed higher 13C-lysine incorporation into myelin proteins in 1- and 4-month-old mice than in 18- and 26-month-old mice.
  • In MS tissue, completely demyelinated chronic lesions rarely contained BCAS1+ oligodendrocytes, whereas partially remyelinated lesions contained clusters highest at the lesion border and within remyelinating areas; BCAS1+ cells were also found in completely inactive lesions.

Methods

  • The study combined antibody validation, immunofluorescence/confocal imaging, transgenic lineage tracing (NG2-CreERT2, PLP-CreERT2, Sox10-CreERT2 × Esco2fl/fl), EdU pulse-chase, lysolecithin- and cuprizone-induced demyelination models, human autopsy and MS lesion tissue, human iPSC-derived oligodendrocytes, and SILAC-based mass spectrometry.
  • Quantitative analyses were performed blinded, with no outlier removal; statistics used GraphPad Prism 6, including Kolmogorov-Smirnov normality testing, t tests or Mann-Whitney tests, and one-way ANOVA with post hoc tests or Kruskal-Wallis with Dunn’s multiple comparison tests.

Limitations

  • Stated: human oligodendroglial morphology, metabolism, and function are less understood than in rodents; remyelination may operate on a different time scale and require additional cues in humans; lineage-tracing dynamics cannot be extrapolated to humans; the lifetime and cellular state of BCAS1+ cells in human brain and MS lesions are unknown, so whether they are newly formed or old cells locked in an intermediate state cannot be determined.
  • Evident: human evidence is largely descriptive immunohistology, with newborn autopsy data from n = 3 and no direct human lineage tracing; the function of BCAS1 itself is unknown.

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Integrity signals

Registry

Crossref · 10.1126/scitranslmed.aam7816

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

7 of 8 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

Show all 75 claims

  • Probably not a substantial claim. 8
  • It may state two separate claims as one. 39
  • The quote only partly states this claim. 1
45 of 45
  • The paper relies on this without support.

    No molecular marker exists that allows discrimination of myelinated from remyelinated axons, and ongoing myelination is difficult to detect, so it has not been possible to determine whether new myelin sheaths are formed in chronically demyelinated MS lesions.

    “Currently, no molecular marker exists that allows the discrimination of myelinated from remyelinated axons, and ongoing myelination is notoriously difficult to detect; consequently, it has thus far not been possible to determine whether new myelin sheaths are formed in chronically demyelinated MS lesions.”
  • The paper relies on this without support.

    Failure of remyelination contributes to disease progression in MS.

    “Because failure of remyelination contributes to disease progression in MS, remyelinating oligodendrocytes might represent an important drug target.”
  • The paper relies on this without support.

    Whether and how brain activity modulates myelin changes is not well understood.

    “However, human studies are often based on magnetic resonance imaging, which does not provide direct information on myelin; therefore, whether and how brain activity modulates myelin changes is not well understood.”
  • The paper relies on this without support.

    Human studies of white matter changes upon learning and training are often based on magnetic resonance imaging, which does not provide direct information on myelin.

    “However, human studies are often based on magnetic resonance imaging, which does not provide direct information on myelin; therefore, whether and how brain activity modulates myelin changes is not well understood.”
  • The paper relies on this without support.

    Remyelinating oligodendrocytes might represent an important drug target in MS.

    “Because failure of remyelination contributes to disease progression in MS, remyelinating oligodendrocytes might represent an important drug target.”
  • The paper relies on this without support.

    The typical chronological sequence of myelination in the human white matter is established.

    “the established typical chronological sequence of myelination in the white matter”
6 of 6

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Metadata

Authors
Fard, M. K., van der Meer, F., Sánchez, P., Cantuti-Castelvetri, L., Mandad, S., Jäkel, S., Fornasiero, E. F., Schmitt, S., Ehrlich, M., Starost, L., Kuhlmann, T., Sergiou, C., Schultz, V., Wrzos, C., Brück, W., Urlaub, H., Dimou, L., Stadelmann, C., & Simons, M.
Affiliations
  • Max Planck Institute of Experimental Medicine (DE)
  • Universitätsmedizin Göttingen (DE)
  • Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
  • Ludwig-Maximilians-Universität München (DE)
  • University Hospital Münster (DE)
  • Max Planck Institute for Molecular Biomedicine (DE)
  • Universität Ulm (DE)
  • German Center for Neurodegenerative Diseases (DE)
Corresponding author
  • Fard, Maryam K.
  • van der Meer, Franziska
  • Stadelmann, Christine
  • Simons, Mikael
Venue
Science Translational Medicine
Published
2017-12-06
Volume
9
Issue
419
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
OpenAlex
W2771504695
Cited by
249
References
49
Citations by year
2026: 35 · 2025: 37 · 2024: 44 · 2023: 36 · 2022: 31 · 2021: 23 · 2020: 24 · 2019: 14 · 2018: 5
FWCI
7.99
Type
journal article
Language
en
Open access
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
  • ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
  • Max Planck Digital Library (submittedVersion, other-oa)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
  • DZNE Pub (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
ERC CoG (award297874, 647168)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords
BCAS1, oligodendrocytes, myelination, remyelination, multiple sclerosis, demyelination, white matter lesions, remyelination therapy
MeSH terms
Animals, Demyelinating Diseases, Humans, Multiple Sclerosis, Myelin Sheath, Neoplasm Proteins, Oligodendroglia, Mice

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