Atypical Cell Cycle Regulation over Neural Stem Cell Expansion

Abstract

Populations of adult neural stem cells (NSCs) that reside in the mammalian brain aid in neurogenesis throughout life and can be identified by a type VI intermediate filament protein, Nestin. Cell cycle regulation plays an important role in maintaining a balance between self-renewal and differentiation and determining the fate of NSCs. Data from our group and others support that the atypical cyclin-like protein Spy1 (also called RingoA; gene SPDYA) 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, increases stemness characteristics, decreases differentiation, and increases susceptibility to oncogenic transformation. 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.