Spatial and cell type transcriptional landscape of human cerebellar development.
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IF: 28.771
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Cited by: 17
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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.

Keywords

LCM-seq
SPLiT-seq
Spatial Transcriptomics

MeSH terms

Cerebellum
Fetus
Humans
Laser Capture Microdissection
Neurogenesis
Single-Cell Analysis
Transcriptome

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

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