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Spatial and cell type transcriptional landscape of human cerebellar development

Lookup NU author(s): Lynne Overman, Dr Steven Lisgo

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Abstract

© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.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.


Publication metadata

Author(s): Aldinger KA, Thomson Z, Phelps IG, Haldipur P, Deng M, Timms AE, Hirano M, Santpere G, Roco C, Rosenberg AB, Lorente-Galdos B, Gulden FO, O'Day D, Overman LM, Lisgo SN, Alexandre P, Sestan N, Doherty D, Dobyns WB, Seelig G, Glass IA, Millen KJ

Publication type: Article

Publication status: Published

Journal: Nature Neuroscience

Year: 2021

Pages: epub ahead of print

Online publication date: 17/06/2021

Acceptance date: 10/05/2021

ISSN (print): 1097-6256

ISSN (electronic): 1546-1726

Publisher: Nature Research

URL: https://doi.org/10.1038/s41593-021-00872-y

DOI: 10.1038/s41593-021-00872-y


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