GSE162047
Neural stem cells alter nucleocytoplasmic partitioning and accumulate nuclear polyadenylated transcripts during quiescence
Quiescence is a cellular state characterized by reversible cell-cycle arrest and diminished biosynthetic activity that protects against environmental insults, replicative exhaustion and proliferation-induced mutations. Entry into and exit from this state controls development, maintenance and repair of tissues, plus in the adult central nervous system, generation of new neurons and thus cognition and mood. Cancer stem cells too can undergo quiescence, which confers them resistance to current therapies. Despite clinical relevance, quiescence lacks understanding and is defined functionally given lack of molecular markers. Inhibition of the Target of Rapamycin pathway is a common denominator of quiescence across species and cell types. This pathway integrates diverse signals towards control of metabolism and cytoskeleton, and lowered pathway activity in quiescence ensures decrease of the most resource-¬intensive cellular process of protein synthesis. Here, we combine Drosophila genetics and a mammalian model to show that altered nucleocytoplasmic partitioning and nuclear bias of a fraction of polyadenylated RNAs are novel evolutionarily conserved mechanisms of quiescence regulation. Altogether, these mechanisms contribute a new regulatory layer to inhibition of protein translation in quiescent cells, whilst likely priming them for quick reactivation in response to appropriate cues. Overall design: In vitro derived primary cultures of mouse hippocampal neural stem cells were either kept in proliferative conditions (0-days in BMP4 or active state: A) or induced into quiescence by exposure to BMP4 for 3 days (Q_3-day) or 10 days (Q 10-days). Nuclear/Cytoplasmic fractionation was performed and total RNA was extracted from each fraction. Four replicates per condition were acquired.