The purinergic receptor P2Y ₁₃ controls the activation and mode of division of adult ventricular–subventricular zone neural stem cells

The ventricular–subventricular zone (V-SVZ) is the most active germinal area in the mammalian brain and it continues to generate newborn neurons throughout life. This area harbors a population of neural stem cells (NSCs) that exist in different states of activation: quiescent NSCs, primed NSCs, and activated NSCs. There are currently few specific markers to effectively discern each state. Likewise, the molecular signals that control the transition from quiescence to activation remain largely unexplored, and the factors that controls whether dividing NSCs differentiate or self-renew are poorly understood. Here, we present evidence that the metabotropic P2Y ₁₃ purinergic receptor plays a critical role in regulating adult neurogenesis. We found that P2Y ₁₃ is specifically expressed in NSCs within the adult V-SVZ and that its levels can be used to distinguish quiescent from activated NSCs. P2Y ₁₃ signaling promotes NSC activation, enhancing lineage progression as opposed to their self-renewal. Conversely, pharmacological blockade or genetic silencing of P2Y ₁₃ receptors favors NSC quiescence. Thus, we consider the metabotropic P2Y ₁₃ purinergic receptor a pivotal modulator of NSC dynamics.