The discovery of adult neurogenesis in mammals changed the long-lasting view of the brain as an immutable structure and raised new hope for brain regeneration. In the past fifty years adult neurogenesis was found in almost all mammals and has been extensively studied in rodents. Adult born neurons have special properties that significantly influence the activity of the networks into which they integrate, playing important roles in memory formation and cognitive flexibility. Furthermore, adult neurogenesis was shown to regulate affective state and to play a role in depression. Despite the vast body of knowledge regarding rodent adult neurogenesis, the data describing it in humans is scarce. Most studies investigating human adult neurogenesis rely on immunohistology, using biomarkers established in rodents. In this study we set out to test the existence of human adult neurogenesis in an unbiased manner by analysing the transcriptome of the cells present in the hippocampus using single nucleus RNA sequencing. One of the main goals of this project was to identify individual neural progenitors in the human brain and to characterize their transcriptome. We also aimed to characterize in detail the stem cell niches using spatial transcriptomics. The Frisén laboratory showed with the help of 14C-birthdating that adult born neurons are integrating not only in the human hippocampus but also in the striatum. However, it is not known where these neurons are originating from and in which striatal structures they are integrating. Thus, we also aim to analyze the human nucleus accumbens, nucleus caudatus and the putamen and to determine if newly generated neurons are present in these structures. Our project aimed to bring a detailed characterization of human neurogenesis, answering important outstanding questions in the field, and to create protocols and datasets that will be the starting points for numerous future studies investigating human adult neurogenesis in physiological and pathological contexts.
