Stem cells from human exfoliated deciduous teeth (SHED) have mitochondrial transfer ability in stromal-derived inducing activity (SDIA) co-culture system.

Stem cells from human exfoliated deciduous teeth (SHED) have stromal-derived inducing activity (SDIA): which means these stromal cells induce neural differentiation where they are used as a substratum for embryonic stem cell (ESCs) culture. Recent studies show that mitochondria or mitochondrial products, as paracrine factors, can be released and transferred from one cell to another. With this information, we were curious to know whether in the SDIA co-culture system, SHED release or donate their mitochondria to ESCs. For this purpose, before co-culture, SHED s' mitochondria and ESCs s' cell membranes were separately labeled with specific fluorescent probes. After co-culture, SHED s' mitochondria were tracked by fluorescent microscope and flow cytometry analysis. Co-culture also performed in the presence of inhibitors that block probable transfer pathways suchlike tunneling nanotubes, gap junctions or vesicles. Results showed that mitochondrial transfer takes place from SHED to ESCs. This transfer partly occurs by tunneling nanotubes and not through gap junctions or vesicles; also was not dependent on intracellular calcium level. This kind of horizontal gene transfer may open a new prospect for further research on probable role of mitochondria on fate choice and neural induction processes.

Correction: A compound downregulation of SRRM2 and miR-27a-3p with upregulation of miR-27b-3p in PBMCs of Parkinson's patients is associated with the early stage onset of disease.

[This corrects the article DOI: 10.1371/journal.pone.0240855.].

Modified level of miR-376a is associated with Parkinson's disease.

Parkinson's disease (PD) is a frequent progressive neurodegenerative disorder. Impaired mitochondrial function is a major feature of sporadic PD. Some susceptibility or causative genes detected in PD are strongly associated with mitochondrial dysfunction including PGC1α, TFAM and GSK3ß. microRNAs (miRNAs) are non-coding RNAs whose altered levels are proven in disparate PD models and human brains. Therefore, the aim of this study was to detect modulations of miRs upstream of PGC1α, TFAM and GSK3ß in association with PD onset and progress. In this study, a total of 33 PD subjects and 25 healthy volunteers were recruited. Candidate miRNA (miR-376a) was selected through target prediction tools and literature survey. Chronic and acute in vitro PD models were created by MPP+ -intoxicated SHSY5Y cells. The levels of miR-376a and aforementioned genes were assessed by RT-qPCR. The expression of target genes was decreased in chronic model while there were dramatically up-regulated levels of those genes in acute model of PD. miR-376a was strongly altered in both acute and chronic PD models as well as PBMCs of PD patients. Our results also showed overexpression of PGC1α, and TFAM in PBMCs is inversely correlated with down-regulation of miR-376a, suggesting that miR-376a possibly has an impact on PD pathogenesis through regulation of these genes which are involved in mitochondrial function. miR-376a expression in PD-derived PBMCs was also correlated with disease severity and may serve as a potential biomarker for PD diagnosis. This is the first study showing altered levels of miR-376a in PD models and PBMCs, suggesting the probable role of this miRNA in PD pathogenesis. The present study also proposed TFAM and PGC1α as target genes of miR-376a for the first time, through which it possibly can exert its impact on PD pathogenesis.

The expression of peroxisomal protein transcripts increased by retinoic acid during neural differentiation.

Peroxisomal matrix protein is mainly expressed in heart, skeletal muscle, and brain tissues. To study the expression of peroxisomal protein (PEP) during neurogenesis, we employed mouse embryonic carcinoma cells (P19) and embryonic stem cells (mESCs) as an in vitro model for neural differentiation by retinoic acid (RA) induction. Expression pattern of PEP was investigated under distinct steps of differentiation by RT-PCR and real-time PCR. The results revealed that expression of PEP transcripts was markedly increased after the RA treatment at embryoid body and neural stages. Therefore, we concluded that PEP might be involved in the early process of neurogenesis, which needs further verification.