| dc.description.abstract | In human brain, most neurons are generated during fetal development, however adult neurogenesis, the lifelong self-renewal of neural stem cells (NSCs) and their maturation into neurons, remains a long-debated topic (Spalding et al., 2013; Kempermann, 2015; Boldrini et al., 2018; Sorrells et al., 2018). In rodents, two neurogenic niches are so far robustly identified, the subventricular zone (SVZ), along the walls of the lateral ventricles, and the subgranular zone (SGZ) of the dentate gyri in the hippocampus (Gage et al., 2000; Gillotin et al., 2021). However, the subgranular zone of the dentate gyrus is the only putatively neurogenic region in the adult human brain. This process is referred to as adult hippocampal neurogenesis (AHN). So far, to address the controversial topic of adult neurogenesis in the human hippocampus, several techniques have been used, such as neuronal birth-dating, marker-based immunohistochemistry and more recently single-nucleus RNA-sequencing (scRNA seq). Even if similar techniques have been employed, different results and conclusions have been reached, pointing towards the challenges and the limitations of the approaches and markers used to investigate this controversial topic in neuroscience. Therefore, it is absolutely necessary to find new and more reliable and specific markers to investigate the presence or the absence of neurogenesis in the adult human brain. The present study aims to address this necessity by focusing on the closest established and characterized neurogenic event to the adult neurogenesis in human, namely the human fetal neurogenesis, which occurs during embryonic development. With this rational, a meta-analysis was performed taking into consideration studies where human fetal brain samples were subjected to scRNA sequencing. The hypothesis behind this study is that neurogenic cell type-specific markers might be conserved between fetal and adult neurogenesis in human (Urbán and Guillemot, 2014). Hence, a list of candidate markers for NSCs, neural progenitor cells (NPCs) and immature neurons (ImNs) was obtained via in silico cross-referencing of previously published single-cell transcriptomic datasets. Subsequently, these candidate markers were further evaluated by analysing their transcriptional profile along the differentiation of two distinct human stem cell lines, induced-pluripotent stem cells (iPSCs) and RenCells, selecting those with an expected expression profile for each specific cell type of interest. In addition, the expression of the selected candidate markers, one for each cell type, was validated via immunofluorescence in the same two human stem cell lines. The final candidate markers were also tested in mouse brain section at two different aging stages, in healthy and Alzheimer’s mouse model brain. Based on our preliminary results, the selected gene sets may offer a useful resource for identifying neurogenic markers conserved in fetal and adult human brain. Yet, further evaluation and validation follow-up studies are necessary, in order to systematically delineate commonalities and differences between embryonic and adult neurogenesis on a quest for more specific neurogenic markers. | |
