Editorial: “Unravelling neural stem cell biology: players and strategies”

The properties and behaviour of adult or somatic neural stem cells (NSCs) are governed by a complex network of intrinsic molecules and pathways along with a milieu of extrinsic signals hailed from the extremely controlled environment or niche in which they reside. These NSCs are able to selfsustain while dividing to produce highly proliferative intermediate progenitors that, in turn, give rise to neuroblasts and neurons. Plasticity in the adult brain is mainly fostered by the generation of new neurons and their functional integration, a process that remains far from being well understood. This phenomenon has been shown to occur in vertebrates: fish, amphibians, reptiles, birds and mammals, with conflicting results regarding humans, leading to a yet unresolved debate. However, a consensusPAGE \* Arabic \* MERGEFORMAT 2This is a provisional file, not the final typeset article exists over the notion that the extent and functional relevance of adult neurogenesis is different throughout vertebrate classes [1].In mammals, adult neurogenesis occurs mainly in the olfactory bulbs and the dentate gyrus of the hippocampus, with neurons arising from lateral ventricle walls-or dentate gyrus-residing NSCs, respectively. Neurogenesis beyond these canonical subependymal (also known as ventricularsubventricular zone or V-SVZ) and hippocampal niches has also been reported but it remains deeply controversial [2]. In this special number, Fernández Acosta et al. follow up previous work [3] and describe the presence and activity of local NSCs in the murine olfactory bulb core, which contribute with new olfactory neurons distinct from those differentiating from neuroblasts that migrate from the lateral ventricle niche, with differential dendrite arborization depending on their final integration position in the periglomerular or the granular layers.Transcriptomic and proteomic analyses have partially decoded NSC molecular signatures and have helped to unveil the complexity of the molecular network of signals that rules NSC biology [4; 5]. Amongst these, extracellular niche cues stand-out as key instructors of NSC cellular decisions. In their review article, Quaresima et al. thoroughly revise the current knowledge on the structure and the peculiarities of the V-SVZ neurogenic niche. They also discuss the contribution of the extracellular signals provided by the niche components to the network with a special emphasis set on ependymal and vascular components of the niche. They discuss the role of signals produced by endothelial cells and pericytes, as well as the involvement of choroid plexus-derived cerebrospinal fluid cues. Finally, the authors consider the possible implications of the latter in pathological situations such as hydrocephalus.Single-cell analysis combined with retrospective isolation has allowed for the first time the identification of NSC in three proliferative states that coexist in the neurogenic niche. Quiescence is a PAGE \* Arabic \* MERGEFORMAT 3 strictly regulated property that allows cells to reversibly exit proliferation. This ability protects NSC pools from eventual exhaustion and DNA damage accumulation through adulthood and is currently regarded as one of the hallmarks of stem cell ageing [6]. To understand the molecular mechanisms ruling NSC entry and exit from quiescence is paramount to fully comprehend the process of adult neurogenesis. Unveiling this process may partly disclose why active and prolific niches correlate This is a provisional file, not the final typeset article specifically in two pallial regions: the caudal lateral pallium and the rostral medial pallium, involving NSCs proliferation and activity-dependent survival. In addition to those already mentioned, in the last decades, increasing evidence has pointed to social behaviour as an additional factor affecting adult neurogenesis. However, if and how do both phenomena influence each other is far from being well understood. In their review, Garcia-Gomez et al. nicely summarise the available evidence about bidirectional relationships between social behaviours and neurogenesis. The authors discuss how neurogenic changes induced either genetically or environmentally influence behaviour, and how social behaviours such as social living conditions, social enrichment, and social stress affect neurogenesis.The regulation of the phenomenon of adult neurogenesis is complex and multifactorial, and affects all stages of the process, from NSC maintenance and self-perpetuation, differentiation into committed progeny, to the migration, survival and functional integration of new-born neurons. This comes as no surprise since being able to orchestrate the correct balance between quiescence and activation to ensure lifelong maintenance of an NSC pool, while producing the proper rate of differentiated progeny to meet the demands of an ever-adapting system as the brain, poses a formidable task. Surely, the list of NSC regulators, both intrinsic and contextual, will continue to expand in the following years as will the resolution and versatility of the techniques to study them.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.