Atypical Cell Cycle Regulation over Neural Stem Cell Expansion

Abstract

SUMMARYPopulations of quiescent adult neural stem cells (NSCs) that reside in the mammalian brain aid in neurogenesis throughout life and can be identified by molecular markers including Nestin, a type VI intermediate filament protein. Cell cycle regulation plays an important role in determining the fate of NSCs in the adult brain and maintaining a crucial balance between self-renewal and differentiation. Data from our group and others support that the atypical cyclin-like protein Spy1 (also called RingoA; geneSPDYA) plays a critical role in activating NSCs from a quiescent state. Elevated levels of Spy1 are found in aggressive human brain cancers, including glioblastoma. Using a conditional mouse model, we demonstrate that driving the expression of Spy1 in the Nestin-enriched NSC population of the brain directs the cells toward symmetric cellular division, increases stemness characteristics, decreases differentiation, and increases susceptibility to oncogenic transformation & drug resistance. This study contributes to better understanding of intricate cell cycle mechanisms which lead to deviation from the homeostatic state, promoting aberrant changes in adult NSCs.