Abstract
BackgroundNeural stem cells (NSCs) are able to differentiate into neurons and astroglia. miRNAs have been demonstrated to be involved in NSC self-renewal, proliferation and differentiation. However, the exact role of miR-124 in the development of NSCs and its underlying mechanism remain to be explored.MethodsPrimary NSCs were isolated from embryos of Wistar rats. Immunocytochemistry was used to stain purified NSCs. miR-124, Delta-like 4 (DLL4), ki-67, Nestin, β-tubulin III, glial fibrillary acidic protein (GFAP), HES1, HEY2, and cyclin D1 (CCND1) expressions were detected by qRT-PCR and western blot. The interaction between miR-124 and DLL4 was confirmed by luciferase reporter assay. Cell proliferation was assessed by MTT assay.ResultsNSCs could self-proliferate and differentiate into neurons and astrocyte. miR-124 was up-regulated and DLL4 was down-regulated during NSC differentiation. DLL4 was identified as a target of miR-124 in NSCs. Ectopic expression of miR-124 or knockdown of DLL4 promoted the proliferation and the formation of NSCs to neurospheres. Moreover, miR-124 overexpression or DLL4 down-regulation improved β-tubulin III expression but decreased GFAP expression in NSCs. Furthermore, enforced expression of DLL4 partially reversed the effects of miR-124 on NSCs proliferation and differentiation. Elevated expression of miR-124 suppressed the expressions of HES1, HEY2, and CCND1 in NSCs, while these effects were attenuated following the enhancement of DLL4 expression.ConclusionmiR-124 promoted proliferation and differentiation of NSCs through inactivating Notch pathway.
Highlights
Neural stem cells (NSCs) are able to differentiate into neurons and astroglia. miRNAs have been demonstrated to be involved in neural stem cells (NSCs) self-renewal, proliferation and differentiation
MiR‐124 expression was increased and Delta-like 4 (DLL4) was decreased during NSC differentiation To determine the roles of miR-124 and DLL4 in NSCs differentiation, the expressions of miR-124 and DLL4 at mRNA and protein levels during NSC differentiation were detected by qRT-PCR and western blot
These data suggested that miR-124 and DLL4 may participate in NSC differentiation
Summary
Neural stem cells (NSCs) are able to differentiate into neurons and astroglia. miRNAs have been demonstrated to be involved in NSC self-renewal, proliferation and differentiation. Neural stem cells (NSCs) are able to differentiate into neurons and astroglia. MiRNAs have been demonstrated to be involved in NSC self-renewal, proliferation and differentiation. The NSCs are a type of multipotent, self-renewal, and undifferentiated neural progenitor cells residing in the subventricular zone (SVZ) of the adult and developing CNS [2]. Increasing studies have highlighted the involvement of miRNAs in neural stem cell self-renewal, development, proliferation and differentiation via control of different stem cell regulators [8,9,10]. Several lines of evidence have suggested that overexpression of miR-124 inhibited proliferation in medulloblastomas and adult neural precursors [13, 14], and induced neuronal differentiation of both progenitor cells [15] and HeLa cells [16]. The molecular mechanisms of miR-124 associated with proliferation and differentiation of NSCs are still unknown
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