Spatial and cell type transcriptional landscape of human cerebellar development.

Abstract

The human neonatal cerebellum is a fourth of its adult size, yet contains the blueprint required to integrate environmental cues with developing motor, cognitive, and emotional skills into adulthood. Although mature cerebellar neuroanatomy is well studied, understanding its developmental origins is limited. Here, we systematically mapped the molecular, cellular, and spatial composition of human fetal cerebellum by combining laser capture microscopy and SPLiT-seq single-nucleus transcriptomics. We profiled functionally distinct regions and gene expression dynamics within cell types and across development. The resulting cell atlas demonstrates that the molecular organization of the cerebellar anlage recapitulates cytoarchitecturally distinct regions and developmentally transient cell types that are distinct from the mouse cerebellum. By mapping genes dominant for pediatric and adult neurological disorders onto our dataset, we identify relevant cell types underlying disease mechanisms. These data provide a resource for probing the cellular basis of human cerebellar development and disease.