Abstract
There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL in vitro. Before transdifferentiation of UMSCs into uNSCLs, high levels of EID3 and low levels of DNMT3A were detected; after transdifferentiation, low levels of EID3 and high levels of DNMT3A were detected. The current work showed that EID3 and DNMT3A co-localized in cell nuclei and EID3 interacted directly with DNMT3A in uNSCL. In summary, these results suggest that DNMT3A is probably directly regulated by EID3 during UMSC transdifferentiation into uNSCLs. These findings indicated a novel mechanism by which EID3, a p300 acetyltransferase inhibitor, could directly affect DNMT3A, this enzyme possesses dual methylation and demethylation abilities. These studies may be helpful for understanding a complex regulation mode of DNMT3A, which is a unique member of the methyltransferase family.
Highlights
Important, it provides a powerful tool for regulating key of stem cell development features such cell fate determination, commitment, and differentiation
Quantitative RT-PCR of uNSCL, mRNA encoding NESTIN, PAX6, VIMENTIN, GFAP, MUSASHI1 and NEUROD1 could be detected at levels between 3- and 13.2-fold those seen in UMSCs (P = 0.018, 0.005, 0.26, 0.0003, 0.017, and 0.002, respectively) (Fig. 2D)
Since mature nerve cells have a limited capacity for self-renewal, neural stem cells (NSCs) play an important role in cell therapy for the treatment of neurodegenerative disorders
Summary
Important, it provides a powerful tool for regulating key of stem cell development features such cell fate determination, commitment, and differentiation. Epigenetic changes of MSC transdifferentiation include chromatin remodeling, histone modification, DNA methylation and microRNA8. DNA methylation is a pivotal mechanism of epigenetic regulation of stem cell reprogramming. Building-up stem cell fates during development depends on de novo DNA methylation catalyzed by DNMT3A and DNMT3B. In studies in mouse embryonic stem cell-derived NPCs, DNMT3A was found to regulate the timing of both differentiation and proliferation. Using real-time quantitative polymerase chain reaction (qRT-PCR) screening of epigenetics-related genes, we discovered that there is a relationship between EID3 and DNMT3A during the process of UMSC to uNSCL transdifferentiation. EID3 directly interacts with DNMT3A and regulates its expression in uNSCL. This raises the interesting question of whether there is a relationship between EID3 and DNMT3A during uNSCL transdifferentiation. Our study gives new insights into the epigenetic mechanisms of MSC transdifferentiation
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