MicroRNA expression profiles of neural stem cells following valproate inducement

Abstract

Neural stem cells (NSCs) possess self-renewal and multilineage differentiation ability, thus are considered to be a potential source for cell replacement therapy of many nervous system diseases, such as neurodegenerative diseases. Valproate (VPA), a member of histone deacetylase inhibitor family, is an epigenetic regulator and can promote NSCs to differentiate into neurons, nevertheless, the underlying mechanisms of the process remain unclear. MicroRNAs (miRNAs) exert a crucial part in the posttranscriptional regulation of gene expression. Epigenetic mechanisms involve in the regulation of miRNAs expression. Therefore we speculated that miRNAs may be important factors during the promotion of neuronal differentiation by VPA. Here, after selecting appropriate concentration and treatment time of VPA, we conducted microRNA arrays at 24 h on the treatment of 1 mM VPA or vehicle. After validation, we obtained 5 significantly upregulated miRNAs (miR-29a-5p, miR-674-5p, miR-155-5p, miR-652-3p, and miR-210-3p) in VPA group compared with control. We predicted the target genes of these miRNAs on the website. Through gene ontology (GO) and pathway analyses, we obtained preliminary comprehension of the function of these genes. The bioinformatics analyses indicated the involvement of them during neurogenesis. In addition, we observed high expression of miR-210-3p, miR-29a-5p, and miR-674-5p in central nervous system, which suggested that they were likely to play crucial roles in neuronal differentiation. We then defined the upregulation of Map2 by transfecting mimic of miR-674-5p, which indicated the promotion of miR-674-5p on NSCs differentiation. The present study explored the miRNAs potentially mediated the function of VPA on promoting NSCs to differentiate into neurons.

Lineage-specific exosomes promote the odontogenic differentiation of human dental pulp stem cells (DPSCs) through TGFβ1/smads signaling pathway via transfer of microRNAs

“…There were 28 microRNAs significantly changed in OD-Exo isolated under odontogenic conditions, of which 7 microRNAs increased (miR-5100, miR-27a-5p, miR-652-3p, miR-1260a, miR-1260b, let-7f-1-3p, and miR-370-3p) and 21 microRNAs decreased (miR-193a-5p, miR-4792, miR-505-3p, miR-629-5p, miR-140-3p, miR-185-5p, miR-146b-5p, miR-339-5p, miR-1246, miR-107, miR-320d, miR-451a, miR-215-5p, miR-126-3p, miR-3687, miR-31-5p, miR-210-3p, miR-1-3p, miR-10a-5p, miR-10b-5p, and miR-619-5p). Among these, 2 upregulated microRNAs (miR-5100 [25], miR-652-3p [26]), and 5 downregulated microRNAs (miR-185-5p [27], miR-107 [28], miR-215-5p [29], miR-31-5p [30], and miR-10b-5p [31]) have been found to play important roles in stem cell differentiation. miR-5100 has been verified to be upregulated during osteoblast differentiation and promoted osteogenic differentiation of MSCs [25].…”

“…miR-5100 has been verified to be upregulated during osteoblast differentiation and promoted osteogenic differentiation of MSCs [25]. miR-652-3p has been found significantly upregulated during neuronal differentiation and might play a pivotal role in the promotion of neuronal differentiation [26]. On the other hand, suppression of miR-185-5p enhanced ameloblast differentiation of LS8 cells and osteogenesis of MC3T3-E1 cells by regulating Dlx2 expression [27].…”

Neural maturation enhanced by exercise-induced extracellular derivatives

“…miR16, -342, -7a, -674, -101, etc. are known to affect neuronal function and have been reported to be involved in energy metabolism [49][50][51][52][53][54][55][56] . miRNAs are known to regulate not only target genes but also their pathways.…”

Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomes

“…The isolation, culture, and differentiation of NSCs were performed as previously described with some modi cations (He et al, 2018). Brie y, pregnant SD rats were anesthetized, and the embryos were removed by cesarean section.…”