Article

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

Department of Genetics, Stanford University School of Medicine
Aging (Impact Factor: 6.43). 02/2011; 3(2):108-24. DOI: 10.18632/aging.100285
Source: PubMed
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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    • "Of particular interest for NSPC regulation, the application of TMS has been linked to changes in the expression of microRNA (miR)-25. Mir-25 has been previously shown to promote neural stem cell proliferation (Brett et al., 2011) by blocking the expression of a cyclin-dependent-kinase inhibitor, p57 (Guo et al., 2014). However the repetitive magnetic stimulation of cultured P3 rat hippocampal neural stem cells, which also enhances their proliferation (≥800 pulses from a 90 mm figure eight coil), is reported to reduce miR-25, but increase miR- 93 and miR-106b (Liu et al., 2015), which instead target the cell cycle regulators integrin-β8 and p21 (Kim et al., 2009; Fang et al., 2011). "
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    • "Of particular interest for NSPC regulation, the application of TMS has been linked to changes in the expression of microRNA (miR)-25. Mir-25 has been previously shown to promote neural stem cell proliferation (Brett et al., 2011) by blocking the expression of a cyclin-dependent-kinase inhibitor, p57 (Guo et al., 2014). However the repetitive magnetic stimulation of cultured P3 rat hippocampal neural stem cells, which also enhances their proliferation (≥800 pulses from a 90 mm figure eight coil), is reported to reduce miR-25, but increase miR- 93 and miR-106b (Liu et al., 2015), which instead target the cell cycle regulators integrin-β8 and p21 (Kim et al., 2009; Fang et al., 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: Transcranial magnetic stimulation (TMS) is widely used in the clinic, and while it has a direct effect on neuronal excitability, the beneficial effects experienced by patients are likely to include the indirect activation of other cell types. Research conducted over the past two decades has made it increasingly clear that a population of non-neuronal cells, collectively known as glia, respond to and facilitate neuronal signalling. Each glial cell type has the ability to respond to electrical activity directly or indirectly, making them likely cellular effectors of TMS. TMS has been shown to enhance adult neural stem and progenitor cell proliferation, but the effect on cell survival and differentiation is less certain. Furthermore there is limited information regarding the response of astrocytes and microglia to TMS, and a complete paucity of data relating to the response of oligodendrocyte-lineage cells to this treatment. However, due to the critical and yet multifaceted role of glial cells in the CNS, the influence that TMS has on glial cells is certainly an area that warrants careful examination.
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    • "The role of miRNAs encoded by the miR-106b-25 cluster has also been linked to growth and maintenance of stem/progenitor cells. High expression of these miRNA was found in bronchioalveolar stem cells from mouse lung [93], neuronal stem/progenitor cells [94] , and nephron progeni- tors [95]. These miRNAs were shown to promote proliferation and maintenance of the bronchioalveolar stem cell pool and to increase survival of nephron progenitor cells through repression of BIM. "
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