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

Abstract

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 MeCP2 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 MeCP2 in neural stem cells. We used two different differentiation methods to explore how MeCP2 influences neural stem cell differentiation. When we transfected MeCP2-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, miR-132 had the largest expression change after differentiation among several central nervous system related miRNAs. A luciferase assay confirmed that miR-132 directly targeted MeCP2, and that miR-132 was able to reduce MeCP2 expression at both the RNA and protein levels. The upregulation of miR-132 by miRNA mimics promoted astrocytic differentiation, which was fully recovered by MeCP2 overexpression. These results indicate that miR-132 regulates cell lineage differentiation by reducing MeCP2. The study was approved by the Ethics Committee of Shanghai Tenth People's Hospital of TongJi University, China (approval No. SHDSYY-2018-4748) on March 10, 2018.