Role of miR-132/methyl-CpG-binding protein 2 in the regulation of neural stem cell differentiation

Methyl-CpG-binding protein 2(MeCP2) is a well-known transcription repressor, and mutations in MECP2 cause serious neurological disorders. Many studies have suggested that Me CP2 is involved in neural maturation only, and have not reported its role in neural stem cell differentiation. In the present study, we investigated this possible role of Me CP2 in neural stem cells. We used two different differentiation methods to explore how Me CP2 influences neural stem cell differentiation. When we transfected Me CP2-overexpressing lentivirus into neural stem cells, astrocytic differentiation was impaired. This impaired astrocytic differentiation occurred even in conditions of 20% fetal bovine serum, which favored astrocytic differentiation. In addition, mi R-132 had the largest expression change after differentiation among several central nervous system related mi RNAs. A luciferase assay confirmed that mi R-132 directly targeted Me CP2, and that mi R-132 was able to reduce Me CP2 expression at both the RNA and protein levels. The upregulation of mi R-132 by mi RNA mimics promoted astrocytic differentiation, which was fully recovered by Me CP2 overexpression. These results indicate that mi R-132 regulates cell lineage differentiation by reducing Me CP2. The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital of Tong Ji University, China(approval No. SHDSYY-2018-4748) on March 10, 2018.