Spatial and cell type transcriptional landscape of human cerebellar development

• Published in: Nature neuroscience Vol. 24; no. 8; pp. 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: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-08-2021; Nature Publishing Group
• Subjects: 631/136; 631/337; 631/337/2019; 631/378; 631/378/2571; Anatomy; Animal Genetics and Genomics; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; 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; Maturation; Motor skill; Neonates; Nervous system diseases; Neurobiology; Neurogenesis; Neurological diseases; Neurosciences; Nuclei (cytology); Pediatrics; Physiological aspects; Resource; Risk factors; Single-Cell Analysis; Transcription; Transcriptome; Transcriptomics; United States
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/s41593-021-00872-y

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.
SPLiT-seq single-nucleus RNA sequencing of the developing human cerebellum reveals cell-type complexities and prolonged maturation compared to mouse with important disease implications.