Spatial and cell type transcriptional landscape of human cerebellar development

Kimberly A. Aldinger, Zachary Thomson, Ian G. Phelps, Parthiv Haldipur, Mei Deng, Andrew E. Timms, Matthew Hirano, Gabriel Santpere, Charles Roco, Alexander B. Rosenberg, Belen Lorente-Galdos, Forrest O. Gulden, Diana O’Day, Lynne M. Overman, Steven N. Lisgo, Paula Alexandre, Nenad Sestan, Dan Doherty, William B. Dobyns, Georg SeeligIan A. Glass, Kathleen J. Millen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalNature neuroscience
Early online dateJun 17 2021
DOIs
StateE-pub ahead of print - Jun 17 2021

Bibliographical note

Funding Information:
This study was funded by the National Institutes of Health under National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development and National Institute of Mental Health grant numbers NS095733 to K.J.M., HD000836 to I.A.G., NS050375 to W.B.D. and MH110926, MH116488 and MH106934 to N.S. The project that gave rise to these results received the support of a fellowship from ‘la Caixa’ Foundation (ID 100010434) to G. Santpere. The fellowship code is LCF/BQ/PI19/11690010. K.A.A. received a Parental Leave Grant from Life Science Editors and would like to thank C. Lilliehook for editorial assistance. This publication is part of the Human Cell Atlas (www.humancellatlas.org/publications).

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

PubMed: MeSH publication types

  • Journal Article

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