Cited by 207Neurogenesis and neuroplasticity mechanismsMicroRNA in disease regulationFOXO transcription factor regulation

The microRNA cluster miR-106b 25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation

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Brett, Jamie O., Renault, Valérie M., Rafalski, Victoria A., Webb, Ashley E., Brunet, Anne·2011·Aging

Abstract

In adult mammals, neural stem cells (NSCs) generate new neurons that are important for specific types of learning and memory. Controlling adult NSC number and function is fundamental for preserving the stem cell pool and ensuring proper levels of neurogenesis throughout life. Here we study the importance of the microRNA gene cluster miR-106b~25 (miR-106b, miR-93, and miR-25) in primary cultures of neural stem/progenitor cells (NSPCs) isolated from adult mice. We find that knocking down miR-25 decreases NSPC proliferation, whereas ectopically expressing miR-25 promotes NSPC proliferation. Expressing the entire miR-106b~25 cluster in NSPCs also increases their ability to generate new neurons. Interestingly, miR-25 has a number of potential target mRNAs involved in insulin/insulin-like growth factor-1 (IGF) signaling, a pathway implicated in aging. Furthermore, the regulatory region of miR-106b~25 is bound by FoxO3, a member of the FoxO family of transcription factors that maintains adult stem cells and extends lifespan downstream of insulin/IGF signaling. These results suggest that miR-106b~25 regulates NSPC function and is part of a network involving the insulin/IGF-FoxO pathway, which may have important implications for the homeostasis of the NSC pool during aging.

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Authors
Brett, J. O., Renault, V. M., Rafalski, V. A., Webb, A. E., & Brunet, A.
Affiliations
Stanford Medicine (US)
Corresponding author
Brunet, Anne
Venue
Aging
Published
2011-02-20
Volume
3
Issue
2
Pages
108-124
ISSN
1945-4589 (ISSN-L)
OpenAlex
W2131928928
Cited by
207
References
108
Citations by year
2026: 2 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 14 · 2019: 21 · 2018: 20 · 2017: 14 · 2016: 15 · 2015: 19 · 2014: 18 · 2013: 29 · 2012: 17
FWCI
7.56
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (CA09302)
  • National Institutes of Health (CA09302)
  • National Institute on Aging (R01AG026648, P01AG036695)
  • National Cancer Institute (5 T32 CA09302, T32CA009302)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
Keywords
miR-25, miR-93, neural stem/progenitor cells, cell proliferation, neuronal differentiation, adult neurogenesis, insulin/IGF-1 signaling, FOXO3, stem cell homeostasis, microRNA regulation
MeSH terms
Forkhead Box Protein O3, Animals, Cell Differentiation, Cells, Cultured, Multigene Family, Insulin, Signal Transduction, Transforming Growth Factor beta, MicroRNAs, Cell Proliferation, Mice, Forkhead Transcription Factors, Neurogenesis, Neural Stem Cells

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