Ph.D Student Jeonbuk National University, Republic of Korea
Abstract: Neural stem cells (NSCs) are progenitor cells capable of self-renewal and differentiation into various neural lineages. The number of neurons in the brain is largely determined by the proliferative potential of NSCs, which is regulated by the frequency of their cell cycle. Although extensive research has been conducted on NSC proliferation and cell cycle regulation, the precise mechanisms remain unclear. The oncogene c-Myc is well-established as a key regulator of cell proliferation and the cell cycle. However, its role in NSC cell cycle regulation has not yet been fully elucidated. Therefore, this study aimed to investigate the role of c-Myc in NSC cell cycle progression. To assess the effects of c-Myc inhibition on NSC viability, cells were treated with the c-Myc inhibitor (10058-F4), and survival rates were analyzed. While no significant changes were observed in embryonic stem cells, NSCs exhibited a marked decrease in viability. Moreover, when the concentration of the inhibitor exceeded 3 μM, NSC survival was significantly reduced. However, apoptosis analysis revealed that treatment with 3 μM of the c-Myc inhibitor did not induce an increase in NSC apoptosis. Cell cycle analysis demonstrated that treatment with 3 μM of the c-Myc inhibitor led to a decrease in the S phase, accompanied by an increase in the G0/G1 and G2/M phases. Additionally, RNA sequencing analysis identified 930 differentially expressed genes, particularly in gene clusters involved in cell proliferation, cell division, and cell cycle regulation. These findings suggest that c-Myc plays a pivotal role in regulating NSC proliferation and cell cycle progression. To further investigate the correlation between KLF2 and transcription factors downregulated by c-Myc inhibition, we performed KLF2 knockdown using shRNA. As a result, NSC proliferation decreased, and the G2/M phase of the cell cycle increased. These findings suggest that c-Myc may regulate NSC cell cycle progression by modulating KLF2 expression.
Funding Source: This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(RS-2024-00410412).
