Cited by 252MicroRNA in disease regulationNeurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene Regulation

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index; 9 of the 19 sources its claims cite were checked for support.

Identification of Dynamically Regulated MicroRNA and mRNA Networks in Developing Oligodendrocytes

Open access

Abstract

MicroRNAs (miRNAs) play important roles in modulating gene expression at the posttranscriptional level. In postnatal oligodendrocyte lineage cells, the miRNA expression profile (“microRNAome”) contains 43 miRNAs whose expression dynamically changes during the transition from A2B5 + oligodendrocyte progenitor cells to premyelinating GalC + cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is downregulated during oligodendrocyte differentiation. In addition, miR-9 expression level inversely correlates with the expression of its predicted targets, among which is the peripheral myelin protein PMP22. We found that PMP22 mRNA but not protein is detectable in oligodendrocytes, whereas Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3′ untranslated region of PMP22 and downregulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This study profiles microRNAs in postnatal rat oligodendrocyte lineage cells and identifies dynamically regulated miRNA–mRNA networks, including a functional interaction between miR-9 and PMP22. It shows that PMP22 mRNA is present in oligodendrocytes but not translated, and that miR-9 down-regulates PMP22 via its 3′UTR.

Key findings

  • 98 miRNAs were reproducibly detected in A2B5+ GalC− oligodendrocyte progenitor cells and A2B5− GalC+ premyelinating oligodendrocytes; 43 miRNAs changed dynamically during differentiation, with 23 down-regulated >2-fold (including miR-9 and miR-124a) and 20 up-regulated >2-fold (including miR-21, miR-152, miR-142-5p/-3p, miR-338, miR-339, and miR-378).
  • Target bias analysis found 37 of 98 miRNAs with target bias in the top or bottom tenth percentile windows; 35 of 37 signatures were negative, while only miR-9 and miR-124a showed positive correlation signatures in oligodendrocytes.
  • PMP22 mRNA was detected in oligodendrocytes and increased ~2-fold during differentiation, but PMP22 protein was not detected in CC1+ oligodendrocytes; Schwann cells lacked mature miR-9 but contained the miR-9 precursor.
  • miR-9 interacted with the PMP22 3′UTR and down-regulated expression: luciferase reporter assays showed ~50% repression (p<0.01), deletion of the AACCAAA repeat blocked miR-9-mediated down-regulation, and miR-9 transfection in Schwann cells reduced PMP22 mRNA by ~30% (p<0.05) with comparable protein reduction (p<0.05).

Methods

  • A2B5+ GalC− OPCs and A2B5− GalC+ oligodendrocytes were FACS-sorted from P7 Sprague-Dawley rat brains; purity was assessed by real-time PCR for neural markers and by CD11b/CD45 FACS analysis.
  • miRNA microarrays and Affymetrix Rat Expression 230 2.0 microarrays were used with four biological replicates; miRNA data were validated by real-time PCR, and target bias was analyzed using TargetScan 4.0 with Fisher’s Exact Test.
  • Functional assays included luciferase reporters containing full-length or fragmented/deleted PMP22 3′UTR in HeLa cells, gelshift assays, and Northern blot, Western blot, and immunofluorescence in rat Schwann cells and postnatal rat brain sections.

Limitations

  • The paper states that its comparison with cortical neuronal cells is preliminary because other neural cells such as neuronal precursors and astrocytes should be included for a more accurate picture.
  • The paper states that 19 additional miRNAs detected by microarray could not be conclusively validated because adequate primers and probes were absent from the multiplex PCR mix.
  • The paper notes that only a few animal miRNA targets are known and that target searches mainly rely on bioinformatic predictions; evident from the text, the miR-9–PMP22 functional validation was performed largely in HeLa and Schwann cells rather than oligodendrocytes, and the target-bias analyses are correlative.

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

Integrity signals

Registry

Crossref · 10.1523/jneurosci.1932-08.2008

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

58 Own result · 19 Own interpretation · 6 No full text of the sources · 5 Own method · 3 Supported · 3 Partly supported · 2 Couldn’t confirm · 2 No basis given · 1 Sources not found · 1 Not checked yet · accuracy not yet measured

Show all 76 claims

  • Probably not a substantial claim. 7
  • It may state two separate claims as one. 19
24 of 24
  • The paper relies on this without support.

    In vivo miRNA expression profiles of defined neural populations have not been reported yet.

    “In vivo miRNA expression profiles of defined neural populations have not been reported yet.”
  • The paper relies on this without support.

    The miRNA expression profiles of specific neural populations (neurons, oligodendrocytes and astrocytes) have not been fully addressed.

    “the miRNA expression profiles of specific neural populations (neurons, oligodendrocytes and astrocytes) have not been fully addressed.”
  • The paper relies on this without support.

    NDRG1 has been previously reported to be expressed in oligodendrocytes and not PMP22.

    “NDRG1 has been previously reported to be expressed in oligodendrocytes and not PMP22, thus making PMP22 an attractive candidate target of miR-9.”
  • The paper relies on this without support.

    miR-9 is enriched in the brain and is conserved during evolution.

    “miR-9 is enriched in the brain and is conserved during evolution, suggesting some important functions in neural cells.”
  • The paper relies on this without support.

    The expression of miR-9 is very high in neuroblasts and glioblasts of fetal brain.

    “The expression of miR-9 is very high in neuroblasts and glioblasts of fetal brain.”
  • The paper relies on this without support.

    The maturation of neuroblasts is associated with a decrease in the expression level of miR-9.

    “Furthermore, the maturation of neuroblasts is associated with a decrease in the expression level of miR-9”
6 of 6

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Metadata

Authors
Lau, P., Verrier, J. D., Nielsen, J. A., Johnson, K. R., Notterpek, L., & Hudson, L. D.
Affiliations
  • National Institutes of Health (US)
  • University of Florida (US)
Corresponding author
Hudson, Lynn D.
Venue
The Journal of Neuroscience
Published
2008-11-05
Volume
28
Issue
45
Pages
11720-11730
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2047606645
Cited by
252
References
44
Citations by year
2026: 3 · 2025: 6 · 2024: 9 · 2023: 12 · 2022: 10 · 2021: 6 · 2020: 11 · 2019: 13 · 2018: 5 · 2017: 16 · 2016: 12 · 2015: 18 · 2014: 25 · 2013: 19 · 2012: 20
FWCI
7.48
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Muscular Dystrophy Association
  • McKnight Foundation
  • Johns Hopkins University
  • European Molecular Biology Laboratory
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS041012, Z01NS002528)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
microRNA, miR-9, oligodendrocyte differentiation, oligodendrocyte precursor cells, PMP22, 3' untranslated region, post-transcriptional regulation, miRNAome, transcriptome, Schwann cells, microRNA target regulation
MeSH terms
Animals, Animals, Newborn, Brain, Cells, Cultured, Galactosylceramides, Gangliosides, Myelin Proteins, Oligodendroglia, RNA, Messenger, Sciatic Nerve, Transfection, Antigens, CD, Rats, Sprague-Dawley, Nonlinear Dynamics, Gene Expression Regulation, Developmental, Computational Biology, MicroRNAs, Microarray Analysis, Green Fluorescent Proteins, Rats

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