FoxO3 Regulates Neural Stem Cell Homeostasis
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In the nervous system, neural stem cells (NSCs) are necessary for the generation of new neurons and for cognitive function. Here we show that FoxO3, a member of a transcription factor family known to extend lifespan in invertebrates, regulates the NSC pool. We find that adult FoxO3(-/-) mice have fewer NSCs in vivo than wild-type counterparts. NSCs isolated from adult FoxO3(-/-) mice have decreased self-renewal and an impaired ability to generate different neural lineages. Identification of the FoxO3-dependent gene expression profile in NSCs suggests that FoxO3 regulates the NSC pool by inducing a program of genes that preserves quiescence, prevents premature differentiation, and controls oxygen metabolism. The ability of FoxO3 to prevent the premature depletion of NSCs might have important implications for counteracting brain aging in long-lived species.
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In NSCs, FOXO3 regulates the size of the NSC pool.
“In NSCs, FOXO3 regulates the size of the NSC pool108.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [108]
NSCs devoid of FOXO3 are defective in self-renewal.
“NSCs devoid of FOXO3 are defective in self-renewal”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [108]
FOXO transcription factors integrate growth factors and stress signal transduction pathways, and may represent a hub for the action of various systemic factors in stem cells in ageing brain, muscle, blood and intestine.
“For example, FOXO transcription factors integrate growth factors and stress signal transduction pathways, and may represent a ‘hub’ for the action of various systemic factors in stem cells in ageing brain, muscle, blood and intestine32,85–90.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [85]
Constitutive deletion of three of the FOXO genes (FOXO1, FOXO3 and FOXO4) in the MuSC lineage during development results in the impairment of postnatal establishment of the MuSC population and a more rapid MuSC depletion with age.
“Consistent with previous reports of the role of FOXO factors in HSC, MuSC and NSC quiescence85–90, constitutive deletion of three of the FOXO genes (FOXO1, FOXO3 and FOXO4) in the MuSC lineage during development results in the impairment of postnatal establishment of the MuSC population and a more rapid MuSC depletion with age32.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [85]
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Self-citationHwang, I., Uchida, H., Dai, Z., Li, F., Sanchez, T., Locasale, J. W., Cantley, L. C., Zheng, H., & Paik, J. (2021) · Nature Communications · doi:10.1038/s41467-020-20839-0 · Cited by 61 · see citing works
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- Authors
- Renault, V. M., Rafalski, V. A., Morgan, A. A., Salih, D. A. M., Brett, J. O., Webb, A. E., Villeda, S. A., Thekkat, P. U., Guillerey, C., Denko, N. C., Palmer, T. D., Butte, A. J., & Brunet, A.
- Affiliations
- Stanford University (US)
- Lucile Packard Children's Hospital (US)
- Stanford Medicine (US)
- Corresponding author
- Brunet, Anne
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 5
- Issue
- 5
- Pages
- 527-539
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC2775802
- OpenAlex
- W1974470246
- Cited by
- 586
- References
- 55
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 33 · 2023: 29 · 2022: 32 · 2021: 42 · 2020: 38 · 2019: 30 · 2018: 39 · 2017: 38 · 2016: 44 · 2015: 48 · 2014: 44 · 2013: 42 · 2012: 37
- FWCI
- 9.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute on Aging (R01AG026648)
- National Cancer Institute (5 T32 CA09302, T32CA009302)
- U.S. National Library of Medicine (R01LM009719, T15LM007033)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- FOXO3, neural stem cells, stem cell homeostasis, self-renewal, quiescence, premature differentiation, oxygen metabolism, gene expression profiling, brain aging, lifespan
- MeSH terms
- Forkhead Box Protein O3, Animals, Brain, Cell Differentiation, Cells, Cultured, Homeostasis, Neurons, Oxygen, Mice, Knockout, Gene Expression Regulation, Developmental, Cell Lineage, Gene Expression Profiling, Mice, Forkhead Transcription Factors, Adult Stem Cells, Neurogenesis
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