1. Spatial and cell type transcriptional landscape of human cerebellar development
- Author
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William B. Dobyns, Georg Seelig, Lynne M. Overman, Forrest O. Gulden, Ian A. Glass, Andrew E. Timms, Ian G. Phelps, Matthew Hirano, Paula Alexandre, Alexander B. Rosenberg, Kathleen J. Millen, Gabriel Santpere, Dan Doherty, Steven Lisgo, Charles M. Roco, Mei Deng, Parthiv Haldipur, Zachary Thomson, Kimberly A. Aldinger, Belen Lorente-Galdos, Diana R. O’Day, and Nenad Sestan
- Subjects
0301 basic medicine ,Cell type ,Cerebellum ,Neurogenesis ,Laser Capture Microdissection ,Biology ,Article ,Transcriptome ,03 medical and health sciences ,Fetus ,0302 clinical medicine ,Single-cell analysis ,medicine ,Humans ,Gene ,Laser capture microdissection ,General Neuroscience ,030104 developmental biology ,medicine.anatomical_structure ,Single-Cell Analysis ,Neuroscience ,030217 neurology & neurosurgery ,Neuroanatomy - 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.
- Published
- 2021