Abstract
In the adult central nervous system (CNS), the subventricular zone (SVZ) of the forebrain is the largest and most active source of neural stem cells (NSCs) that generates mainly neurons and few glial cells lifelong. A large body of evidence has shed light on the distinct families of signaling ligands (i.e., morphogens, growth factors, secreted molecules that alter signaling pathways) in regulating NSC biology. However, most of the research has focused on the mRNA expression of individual or few signaling ligands and their pathway components in specific cell types of the CNS in the context of neurogenesis. A single unifying study that underlines the expression of such molecules comprehensively in different cell types in spatial contexts has not yet been reported. By using whole genome transcriptome datasets of individual purified cell specific populations of the adult CNS, the SVZ niche, NSCs, glial cells, choroid plexus, and performing a bioinformatic meta-analysis of signaling ligands, their expression in the forebrain was uncovered. Therein, we report that a large plethora of ligands are abundantly expressed in the SVZ niche, largely from the vasculature than from other sources that may regulate neurogenesis. Intriguingly, this sort of analysis revealed a number of ligands with unknown functions in neurogenesis contexts that warrants further investigations. This study therefore serves as a framework for investigators in the field for understanding the expression patterns of signaling ligands and pathways regulating neurogenesis.
Highlights
In the adult brain, the subventricular zone (SVZ) of the lateral ventricles is one of the main reservoirs of adult neural stem cells (NSCs) that generate new neurons and glial cells throughout life
Using these datasets we performed an analysis to examine transcripts that are significantly altered across these groups taking into account recent gene lists of exclusively secreted signaling ligands, inhibitory signaling molecules, morphogens and trophic factors (Azim et al, 2017), resulting in 310 probes in total that were ≤5% false discovery rate (FDR)
principle components analysis (PCA) was done against significant probes (Figure 1A), which designated all glial cells, pericytes, transiently amplifying progenitors (TAPs) and neuroblasts exhibiting similar hallmarks, whereas quiescent neural stem cells (qNSCs) and activated NSCs (aNSCs) as well as the choroid plexus (CP) were unrelated
Summary
The subventricular zone (SVZ) of the lateral ventricles is one of the main reservoirs of adult neural stem cells (NSCs) that generate new neurons and glial cells throughout life. The SVZ is located around a spatially complex ventricular system and consists of a heterogeneous cell population, as a number of studies have identified that specific neuronal and glial subtypes are generated from discrete domains of the SVZ throughout life (reviewed in Fiorelli et al, 2015; Azim et al, 2016) This implies that regionally segregated NSCs are primed in a time-controlled manner for the generation of glial and neuronal subtypes, proposing that transcriptional mechanisms are modulated by external stimuli that guide NSC fate. Such add-on regulators include microRNAs, exosomes containing proteins or RNAs, extracellular matrix constituents, additional and soluble secreted factors reviewed in Wakabayashi et al (2014), Batiz et al (2015), and Faissner and Reinhard (2015), the latter being one of the most studied in the field
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