Cited by 122MicroRNA in disease regulationSchizophrenia research and treatmentNeurogenesis and neuroplasticity mechanisms

Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells

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Topol, Aaron, Zhu, Shijia, Hartley, Brigham J., English, Jane, Hauberg, Mads E., Tran, Ngoc, Rittenhouse, Chelsea Ann, Simone, Anthony +16 more·2016·Cell Reports

Abstract

Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq)-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.

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Crossref · 10.1016/j.celrep.2016.03.090

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  • Traditional methods such as GSEA overestimated the number of significant transcription factors, largely confounded by the large number of overlaps among putative target genes of different TFs.

    “However, as we observed in our previous study53, traditional methods such as Gene Set Enrichment Analysis (GSEA) overestimated the number of significant transcription factors, largely confounded by the large number of overlaps among putative target genes of different TFs54.”

    From Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease (2023) · cites this paper as [53]

    In Results, under “miR-9 targets enriched for differentially expressed genes in SZ NPCs” (page unavailable), the paper warns that an enrichment analysis produced a very large list of significant miRNAs, likely confounded by overlapping predicted targets. It identifies the method as Partek Genomics Suite, not GSEA, and discusses miRNAs, not transcription factors; the cited passage therefore does not establish the claim about GSEA overestimating significant TFs. (LLM, conf=0.86)

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Authors
Topol, A., Zhu, S., Hartley, B. J., English, J., Hauberg, M. E., Tran, N., Rittenhouse, C. A., Simone, A., Ruderfer, D. M., Johnson, J., Readhead, B., Hadas, Y., Gochman, P. A., Wang, Y.-C., Shah, H., Cagney, G., Rapoport, J., Gage, F. H., Dudley, J. T., Sklar, P., Mattheisen, M., Cotter, D., Fang, G., & Brennand, K. J.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Royal College of Surgeons in Ireland (IE)
  • Aarhus University (DK)
  • Salk Institute for Biological Studies (US)
  • National Institutes of Health (US)
  • University College Dublin (IE)
Corresponding author
  • Fang, Gang
  • Brennand, Kristen J.
Venue
Cell Reports
Publisher
Elsevier BV
Published
2016-05
Volume
15
Issue
5
Pages
1024-1036
ISSN
2211-1247 (ISSN-L)
OpenAlex
W2342348020
Cited by
122
References
41
Citations by year
2026: 3 · 2025: 4 · 2024: 7 · 2023: 4 · 2022: 14 · 2021: 16 · 2020: 16 · 2019: 11 · 2018: 22 · 2017: 18 · 2016: 7
FWCI
8.06
Type
journal article
Language
en
Update notices
erratum (2017-09-05)
Open access
Locations
  • Cell Reports (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Brain and Behavior Research Foundation
  • New York Stem Cell Foundation (R01 GM114472, R01 MH097276)
  • Icahn School of Medicine at Mount Sinai
  • Health Research Board
  • National Institutes of Health (R01 MH101454, R01 MH106056)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
schizophrenia, miR-9, neural progenitor cells, neuronal migration, microRNA dysregulation, miRNA target genes, disease risk, patient-derived cells
MeSH terms
Cell Movement, Gene Expression Regulation, Humans, Models, Biological, Neurons, Schizophrenia, Transcription Factors, Case-Control Studies, Proteome, Gene Expression Profiling, MicroRNAs, Genetic Association Studies, Induced Pluripotent Stem Cells, Neural Stem Cells, Molecular Sequence Annotation

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