SUMMARY

Populations 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; 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 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.