LEVERAGING SPATIAL TRANSCRIPTOMICS AND MACHINE LEARNING TO CRACK THE SPATIAL CODE OF NEURAL STEM CELL NICHES IN THE ADULT BRAIN

Stem cells are the pillar of tissue repair and regeneration in adults. In the mouse brain, only two specific zones, remnants of embryonic neurogenic regions, retain the ability to proliferate in the adult brain: the Ventricular-Sub-Ventricular Zone (V-SVZ) and the Sub-Granular Zone (SGZ) of the hippocampal Dentate Gyrus (DG). Neural Stem Cells (NSCs) in the Dentate Gyrus produce local excitatory granule neurons involved in spatial memory and mood regulation. In the V-SVZ, NSCs give rise to young neuroblasts that migrate to the Olfactory Bulb (OB) and mature into inhibitory interneurons, which are implicated in olfactory learning and discrimination. In both V-SVZ and DG, NSCs are of glial nature and interact with highly similar niche cell types, including endothelial cells, microglia and oligodendrocytes. NSCs exist in both quiescent and actively dividing states. Beyond differences in division rates, NSCs in the V-SVZ, and possibly in the DG, exhibit regional and molecular diversity, leading to the generation of distinct subtypes of adult-born interneurons. However, it remains unclear whether NSCs in specific niche regions are intrinsically distinct or if their behavior is influenced by extrinsic factors tied to the regionalized nature of the niches themselves. By leveraging spatial transcriptomics, advanced data analysis methods and machine learning, this research aims at comparing the spatial transcriptomics landscapes of the two neurogenic niches of the adult brain at subcellular resolution, to find shared and distinct molecular mechanisms of adult neurogenesis. The main goal is to investigate whether the V-SVZ and SGZ niches cross-talk and synchronize during pregnancy.