Spatial and cell type transcriptional landscape of human cerebellar development

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...

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Bibliographic Details
Published in:	Nature neuroscience 2021-08, Vol.24 (8), p.1163-1175
Main Authors:	Aldinger, Kimberly A, Thomson, Zachary, Phelps, Ian G, Haldipur, Parthiv, Deng, Mei, Timms, Andrew E, Hirano, Matthew, Santpere, Gabriel, Roco, Charles, Rosenberg, Alexander B, Lorente-Galdos, Belen, Gulden, Forrest O, O'Day, Diana, Overman, Lynne M, Lisgo, Steven N, Alexandre, Paula, Sestan, Nenad, Doherty, Dan, Dobyns, William B, Seelig, Georg, Glass, Ian A, Millen, Kathleen J
Format:	Article
Language:	eng
Subjects:	Anatomy Brain research Cell development (Biology) Cerebellum Cerebellum - embryology Cognitive ability Development and progression Fetus Fetuses Gene expression Gene mapping Gene sequencing Genetic aspects Genetic transcription Growth Health aspects Humans Laser Capture Microdissection Motor skill Neonates Nervous system diseases Neurogenesis Neurological diseases Nuclei (cytology) Pediatrics Physiological aspects Risk factors Single-Cell Analysis Transcription Transcriptome Transcriptomics
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Summary:	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.
ISSN:	1097-6256 1546-1726