Reference

Mari Sepp*, Kevin Leiss*, Florent Murat, Konstantin Okonechnikov, Piyush Joshi, Evgeny Leushkin, Lisa Spänig, Noe Mbengue, Céline Schneider, Julia Schmidt, Nils Trost, Maria Schauer, Philipp Khaitovich, Steven Lisgo, Miklós Palkovits, Peter Giere, Lena M. Kutscher, Simon Anders, Margarida Cardoso-Moreira, Ioannis Sarropoulos*, Stefan M. Pfister* & Henrik Kaessmann* Cellular development and evolution of the mammalian cerebellum, Nature 2023 Link to the paper

The expansion of the neocortex, a hallmark of mammalian evolution, was accompanied by an increase in cerebellar neuron numbers. However, little is known about the evolution of the cellular programs underlying cerebellum development in mammals. In this study, we generated single-nucleus RNA-sequencing data for ~400,000 cells to trace cerebellum development 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, where 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 programs have been 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. Altogether, our study unveils shared and lineage-specific programs governing the development of cerebellar cells, and expands our understanding of mammalian brain evolution.

Please see the corresponding app by the Pfister lab (DKFZ, KiTZ) for the analyses of the human data in the context of childhood brain tumors

Methodology

Single-nucleus RNA sequencing data were generated from frozen cerebellum samples obtained from humans, mice, and opossums at various developmental stages. Data were produced using 10x Genomics Chromium Single Cell 3' Gene Expression reagents (version 2 and 3).

Data & code access

You can download SingleCellExperiment objects using the links below. The data is fully annotated. Only the pre-mRNA counting based objects contain the UMAP and LIGER embeddings.

Abbreviations of the cell type categories

Raw sequencing data is available at heiDATA.

The source code of this app can be found here.

Custom code used in the paper is available on gitlab.

Our data on CELLxGENE .

Combined embedding

Contact

If you have issues or find bugs, please report them via mail or via gitlab.

Furthermore, feel free to contact us via mail: Mari Sepp , Nils Trost

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