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Lookup NU author(s): Dr Steven LisgoORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s).The expansion of the neocortex, a hallmark of mammalian evolution 1,2, was accompanied by an increase in cerebellar neuron numbers 3. However, little is known about the evolution of the cellular programmes underlying the development of the cerebellum in mammals. In this study we generated single-nucleus RNA-sequencing data for around 400,000 cells to trace the development of the cerebellum from early neurogenesis to adulthood in human, mouse and the marsupial opossum. We established a consensus classification of the cellular diversity in the developing mammalian cerebellum and validated it by spatial mapping in the fetal human cerebellum. Our cross-species analyses revealed largely conserved developmental dynamics of cell-type generation, except for Purkinje cells, for which we observed an expansion of early-born subtypes in the human lineage. Global transcriptome profiles, conserved cell-state markers and gene-expression trajectories across neuronal differentiation show that cerebellar cell-type-defining programmes have been overall preserved for at least 160 million years. However, we also identified many orthologous genes that gained or lost expression in cerebellar neural cell types in one of the species or evolved new expression trajectories during neuronal differentiation, indicating widespread gene repurposing at the cell-type level. In sum, our study unveils shared and lineage-specific gene-expression programmes governing the development of cerebellar cells and expands our understanding of mammalian brain evolution.
Author(s): Sepp M, Leiss K, Murat F, Okonechnikov K, Joshi P, Leushkin E, Spanig L, Mbengue N, Schneider C, Schmidt J, Trost N, Schauer M, Khaitovich P, Lisgo S, Palkovits M, Giere P, Kutscher LM, Anders S, Cardoso-Moreira M, Sarropoulos I, Pfister SM, Kaessmann H
Publication type: Article
Publication status: Published
Journal: Nature
Year: 2024
Volume: 625
Pages: 788–796
Online publication date: 29/11/2023
Acceptance date: 21/11/2023
Date deposited: 22/01/2024
ISSN (print): 0028-0836
ISSN (electronic): 1476-4687
Publisher: Nature Research
URL: https://doi.org/10.1038/s41586-023-06884-x
DOI: 10.1038/s41586-023-06884-x
Data Access Statement: The datasets generated in the current study are available in the heiDATA repository, https://doi.org/10.11588/data/QDOC4E. Processed data can be interactively explored at https://apps.kaessmannlab.org/sc-cerebellum-transcriptome. Mouse and human processed data are also available as a CELLxGENE collection at https://cellxgene.cziscience.com/collections/72d37bc9-76cc-442d-9131-da0e273862db. Previously published cerebellum snRNA-seq datasets are available at https://singlecell.broadinstitute.org/single_cell/study/SCP795 (Kozareva et al.7), https://www.covid19cellatlas.org/aldinger20/ (Aldinger et al.13), and https://github.com/linnarsson-lab/developing-human-brain (Braun et al.22); and gnomAD LOEUF metrics39 (v2.1.1) at https://gnomad.broadinstitute.org/downloads#v2-constraint. Custom code is available at https://gitlab.com/kaessmannlab/mammalian-cerebellum.
PubMed id: 38029793
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