Abstract
BackgroundSmall non-coding microRNA RNA molecules can regulate stem cell function. The role of microRNAs in neural stem/progenitor cells (NS/PCs) differentiation is not entirely clear.MethodsMiRNA profiling, loss and gain of function studies coupled with dendritic tree development morphometric analysis and calcium influx imaging were utilized to investigate the role of micoRNA-223 in differentiating NS/PCs.ResultsMiRNA profiling in human NS/PCs before and after differentiation in vitro reveals modulation of miRNAs following differentiation of NS/PCs. MiR-223, a microRNA well characterized as a hematopoietic-specific miRNA was identified. Cell-autonomous inhibition of miR-223 in the adult mouse dentate gyrus NS/PCs led to a significant increase in immature neurons soma size, dendritic tree total length, branch number per neuron and complexity, while neuronal migration in the dentate gyrus remained unaffected. Overexpression of miR-223 decreased dendritic tree total length, branch number and complexity in neurons differentiated from human embryonic stem cells (hESCs). Inhibition of miR-223 enhanced N-methyl-D-aspartate (NMDA) induced calcium influx in human neurons differentiated from NS/PCs.ConclusionsTaken together, these findings indicate that miR-223 regulates the differentiation of neurons derived from NS/PCs.Electronic supplementary materialThe online version of this article (doi:10.1186/2052-8426-2-18) contains supplementary material, which is available to authorized users.
Highlights
Small non-coding microRNA RNA molecules can regulate stem cell function
Further gene ontology analysis suggested that miR-223’s potential targets regulate important functions such as cell adhesion, neuron projection development, synapses, and cytoskeleton organization, but not cell migration or protein ubiquitination (Figure 1D and Additional file 1: Dataset S1). These results suggest that miR-223 is expressed during neural stem/progenitor cells (NS/PCs) differentiation and that it could regulate immature neuron morphogenesis and function
Received: 31 October 2013 Accepted: 28 May 2014 Published: 17 June 2014. These data suggest that miR-223 regulates soma size development, dendrite total length, branch number and complexity as well as neuronal activity
Summary
Small non-coding microRNA RNA molecules can regulate stem cell function. The role of microRNAs in neural stem/progenitor cells (NS/PCs) differentiation is not entirely clear. Regulation of protein translation plays an important role in the development of neural circuits; neural differentiation, dendrite development, synaptic plasticity and neural excitability [4]. MicroRNAs (miRNAs) are conserved small untranslated RNA molecules, which regulate protein synthesis. MicroRNAs play major roles in stem cell proliferation [6] and differentiation [7]. Multiple studies demonstrate the importance of miRNAs in the regulation of specific NS/PCs functions. MiR-9, another neuronal specific miRNA specifies sensory organ precursors in Drosophila [10], and is involved in regulation of NS/ PCs proliferation [11]. The role of microRNAs and the full range of microRNAs involved in the regulation of dendritic tree development remain poorly characterized
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