Nac-1 is required for maintenance of multipotency in neural stem/progenitor cells / 西安交通大学学报(医学版)

ABSTRACT

Objective: To study the regulatory mechanism of Nac-1 on the self-renewal of neural stem/progenitor cells (NSPCs). Methods: The expression level of Nac-1 was detected by using ESCs-derived NSPCs as the cell model. RNA interference was used to reduce the expression of Nac-1; the interference efficiency was detected by quantitative RT-PCR and Western blot. The proliferation and apoptosis of NSPCs were detected by cell counting and flow cytometry. Luciferase assay was used to detect the transcriptional regulation of Nac-1 on c-Myc. Results: Nac-1 was highly expressed in NSPCs, and its mRNA level decreased by 77% after differentiation. Compared with that in the control group, the mRNA level of Nac-1 in the NSPCs of the experimental group was significantly decreased, and the interference efficiency was 69% and 66%, respectively. NSPCs with Nac-1 knockdown showed slow proliferation, increased apoptosis and tended to differentiate, and the mRNA level of c-Myc decreased by 46% and 57% in two Nac-1 knockdown groups, respectively. Luciferase assay showed that the transcriptional activity of c-Myc promoter decreased by 24% and 36%, respectively, suggesting that Nac-1 could regulate the promoter activity of c-Myc gene. Conclusion: Nac-1 can promote the proliferation of NSPCs and inhibit their differentiation by regulating the transcription of c-Myc.