Cellular development and evolution of the mammalian cerebellum [Research Data]

Version 3.0

Sepp, Mari; Leiss, Kevin; Murat, Florent; Okonechnikov, Konstantin; Joshi, Piyush; Leushkin, Evgeny; Spänig, Lisa; Mbengue, Noe; Schneider, Céline; Schmidt, Julia; Trost, Nils; Schauer, Maria; Khaitovich, Philipp; Lisgo, Steven; Palkovits, Miklós; Giere, Peter; Kutscher, Lena M.; Anders, Simon; Cardoso-Moreira, Margarida; Sarropoulos, Ioannis; Pfister, Stefan M.; Kaessmann, Henrik, 2021, "Cellular development and evolution of the mammalian cerebellum [Research Data]", https://doi.org/10.11588/data/QDOC4E, heiDATA, V3

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Description	The expansion of the neocortex, a hallmark of mammalian evolution1,2, was accompanied by an increase in cerebellar neuron numbers3. 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 a 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 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. Altogether, our study unveils shared and lineage-specific gene expression programs governing the development of cerebellar cells, and expands our understanding of mammalian brain evolution. (2023-06-23)
Subject	Medicine, Health and Life Sciences
Keyword	single-nucleus RNA sequencing, cerebellum, development, evolution, transcriptomics, smFISH
Related Publication	Sepp, Leiss et al. "Cellular development and evolution of the mammalian cerebellum." doi: 10.1038/s41586-023-06884-x
License/Data Use Agreement	Custom Dataset Terms

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Citation Metadata

Persistent Identifier	doi:10.11588/data/QDOC4E
Publication Date	2021-12-03
Title	Cellular development and evolution of the mammalian cerebellum [Research Data]
Author	Sepp, Mari (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Leiss, Kevin (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Murat, Florent (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Okonechnikov, Konstantin (Hopp-Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany) Joshi, Piyush (Hopp-Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany) Leushkin, Evgeny (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Spänig, Lisa (Hopp-Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany) Mbengue, Noe (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Schneider, Céline (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Schmidt, Julia (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Trost, Nils (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Schauer, Maria (Museum für Naturkunde Berlin, Leibniz Institute for Evolution and Biodiversity Science) Khaitovich, Philipp (Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology, Moscow, Russia) Lisgo, Steven (Biosciences Institute, Newcastle University, Newcastle, UK) Palkovits, Miklós (Human Brain Tissue Bank, Semmelweis University, Budapest, Hungary) Giere, Peter (Museum für Naturkunde Berlin, Leibniz Institute for Evolution and Biodiversity Science) Kutscher, Lena M. (Hopp-Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany) Anders, Simon (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Cardoso-Moreira, Margarida (Evolutionary Developmental Biology Laboratory, Francis Crick Institute, London NW1 1AT, UK) Sarropoulos, Ioannis (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Pfister, Stefan M. (Hopp-Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany) Kaessmann, Henrik (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH))
Point of Contact	Use email button above to contact. Kaessmann, Henrik (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Leiss, Kevin (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)) Sepp, Mari (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH))
Description	The expansion of the neocortex, a hallmark of mammalian evolution1,2, was accompanied by an increase in cerebellar neuron numbers3. 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 a 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 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. Altogether, our study unveils shared and lineage-specific gene expression programs governing the development of cerebellar cells, and expands our understanding of mammalian brain evolution. (2023-06-23)
Subject	Medicine, Health and Life Sciences
Keyword	single-nucleus RNA sequencing cerebellum development evolution transcriptomics smFISH
Topic Classification	evolution, development, cerebellum
Related Publication	Sepp, Leiss et al. "Cellular development and evolution of the mammalian cerebellum." doi: 10.1038/s41586-023-06884-x https://www.nature.com/articles/s41586-023-06884-x
Funding Information	European Research Council: 615253, OntoTransEvol European Research Council: 101019268, VerteBrain European Research Council: 819894, BRAIN-MATCH Brain Research Program: 2017-1.2.1-NKP-2017-00002 Cancer Research UK: FC011171 UK Medical Research Council: FC011171 Wellcome Trust: FC011171
Data Type	snRNA-seq, smFISH

Life Sciences Metadata

Design Type	Not Specified
Factor Type	Cell Type/Cell Line; Developmental Stage; Organism
Organism	Homo sapiens; Mus musculus
Other Organism	Monodelphis domestica
Measurement Type	transcription profiling
Technology Type	nucleotide sequencing
Other Technology Type	single-nucleus RNA sequencing, single molecule FISH
Technology Platform	Illumina
Other Technology Platform	10x Chromium 3' GEX, Resolve Biosciences Molecular Cartography

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