Molecular and spatial design of human cerebellar development

Human cerebellar development is precisely orchestrated by molecular regulatory networks. Here, we combined single-cell transcriptomics, spatial transcriptomics and chromatin accessibility states to systematically depict an integrative temporal-spatial landscape of human fetal cerebellar development. The multiomic data reveal molecular networks, providing an informative regulatory map to show how and when cell fates are determined. Spatial transcriptomics illustrated the distinct molecular signatures of the progenitors, Purkinje cells and granule cells located in different regions of the developing cerebellar cortex. We identified RORB as a new marker of developing human Purkinje cells, which was not expressed in mice. In addition, the RL progenitors highly expressed the human-specific gene ARHGAP11B , and ARHGAP11B expression led to cerebellar cortex expansion and folding in mice. We finally mapped the genes and single-nucleotide polymorphisms (SNPs) of diseases related to cerebellar dysfunction onto cell types, indicating the cellular basis and possible pathogenesis mechanisms of neuropsychiatric disorders. Gestational week 12 to 27 10x Genomics Visium sequencing for more 50,000 nucleis from human fetal cerebellum.