FoxO3 regulates neural stem cell homeostasis

By V. Renault, Victoria A. Rafalski, Alexander A. Morgan, Dervis A M Salih, Jamie O. Brett, A. Webb, Saul A. Villeda, Pramod U. Thekkat, Camille Guillerey, N. Denko and 3 more. 2009

592 citations recorded by the source corpus.

Summary In the nervous system, neural stem cells (NSC) 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 NSC in vivo than wild type counterparts. NSC 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 NSC 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 NSC might have important implications for counteracting brain aging in long-lived species.

Subfields: Aging, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. J. Campisi
2. Jan H. J. Hoeijmakers
3. R. DePinho
4. Y. Fouad
5. C. Aanei

In Molecular Biology

1. R. DePinho
2. Jeroen Essers
3. Fred H. Gage
4. J. Campisi
5. Jan H. J. Hoeijmakers
6. W. V. van Cappellen
7. Erik H. W. Meijering
8. M. Demaria

Citations in the corpus

• The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Table 1 Signals regulating adult hippocampal neurogenesis Stages Regulators Secreted factors and downstream effectors (Morphogens, growth fa”
• Metabolic Plasticity in Stem Cell Homeostasis and Differentiation (2012, unknown): “Nutrient-sensitive signaling pathways that regulate lifespan and energy metabolism, such as those mediated by AMPK, FOXO, insulin/IGF1, and mTOR, impact stem cell function (Jasper and Jones, 2010; Renault et al., 2009).”
• Redox regulation of FoxO transcription factors (2015, background): “Analyses of gene expression profiles showed that FoxO3a regulates genes involved in cellular quiescence, differentiation, oxygen metabolism and antioxidants [290].”
• Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging (2017, background): “FOXO1 and FOXO3 are essential to numerous endogenous processes as development, differentiation, and tumor suppression, roles not prominently attributed to FOXO4 (Hosaka et al., 2004; Nakae et al., 2003; Paik et al., 2007; Renault et al., 2009).”
• FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis (2009, background): “…an accompanying article shows that deletion of FoxO3 alone in the brain via an independent Cre-deletor transgenic line, Nestin-Cre, which allows deletion in NSCs (as well as other cell types), also produces similar decline in NSC number both in vivo and in vitro (Renault et al., 2009, this issue).”