Modelling human adult V-SVZ niche assembly and ependymal cell generation in brain organoids.

The V-SVZ niche is vital for adult neurogenesis in mammals, yet its regulation in humans remains poorly understood. Current models, including brain organoids, fail to replicate the unique cytoarchitecture of this niche, particularly the multiciliated ependymal cells, which are essential for its function and organization. Here, we utilize GEMC1 and MCIDAS to program human apical radial glial cells into ependymal cells, employing human brain organoids as a model. This approach induces premature ependymal cell differentiation and reorganization of the embryonic neurogenic niche, conferring characteristics of the human adult V-SVZ niche. Our findings highlight a molecular pathway that leads to ependymal cell generation and adult human V-SVZ niche reconstruction, providing a platform to study its development and function.