Spatial and cell type transcriptional landscape of human cerebellar development
Kimberly A. Aldinger, Zachary Thomson, Ian G. Phelps, Parthiv Haldipur, Mei Deng, Andrew E. Timms, Matthew Hirano, Gabriel Santpere, Charles Roco, Alexander B. Rosenberg, Belen Lorente-Galdos, Forrest O. Gulden, Diana O’Day, Lynne M. Overman, Steven N. Lisgo, Paula Alexandre, Nenad Sestan, Dan Doherty, William B. Dobyns, Georg Seelig, Ian A. Glass, Kathleen J. Millen
Abstract
The human neonatal cerebellum is one-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 of its developmental origins is limited. In this study, 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.
Datasets
1. Cerebellum
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Source data
https://cellxgene.cziscience.com/collections/1b014f39-f202-45ae-bb7d-9286bddd8d8b
Alias names
phs001908.v2.p1, PMID34140698, PMC8338761
Cite this study
Aldinger, K.A., Thomson, Z., Phelps, I.G., Haldipur, P., Deng, M., Timms, A.E., Hirano, M., Santpere, G., Roco, C., Rosenberg, A.B. and Lorente-Galdos, B., 2021. Spatial and cell type transcriptional landscape of human cerebellar development. Nature neuroscience, 24(8), pp.1163-1175. https://doi.org/10.1038/s41593-021-00872-y