Journal Article

Cellular development and evolution of the mammalian cerebellum

Giere, Peter, National Center for Tumor Diseases - Deutsches Krebsforschungszentrum [Heidelberg, Allemagne] (NCT / DKFZ), Leushkin, Evgeny, Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ) ; German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], Laboratoire de Physiologie et Génomique des Poissons = Fish Physiology and Genomics Institute (LPGP) ; Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Anders, Simon, Lisgo, Steven, Murat, Florent, German Cancer Consortium [Heidelberg] (DKTK), Sepp, Mari, Schmidt, Julia, Pfister, Stefan, Cardoso-Moreira, Margarida, Semmelweis University [Budapest], Okonechnikov, Konstantin, Joshi, Piyush, Leiss, Kevin, Newcastle University [Newcastle], Heidelberg University Hospital [Heidelberg], Trost, Nils, Kaessmann, Henrik, Khaitovich, Philipp

2024

Overview

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. Single-nucleus RNA-sequencing data from the cerebellum of human, mouse and opossum is used to analyse the developmental dynamics of cell types and states in mammalian cerebellum and provide evolutionary insights.

• Publisher: Nature Publishing Group,HAL CCSD,Nature Publishing Group UK
• Subject: 38 / 38/39 / 38/91 / 45 / 631/181/2806 / 631/378/2571/2573 / Animals / Biological evolution / Cell differentiation / Cell Lineage - genetics / Cells / Cerebellum / Cerebellum - cytology / Cerebellum - embryology / Cerebellum - growth & development / Cerebral cortex / Datasets / Evolution / Evolution & development / Evolution, Molecular / Fetus - cytology / Fetus - embryology / Fetuses / Gene expression / Gene Expression Regulation, Developmental / Gene sequencing / Genes / Humanities and Social Sciences / Humans / Life Sciences / Mammals / Mammals - embryology / Mammals - growth & development / Mice / multidisciplinary / Neocortex / Neurogenesis / Neurogenesis - genetics / Neurons / Neurons - cytology / Neurons - metabolism / Opossums - embryology / Opossums - growth & development / Purkinje cells / Purkinje Cells - cytology / Purkinje Cells - metabolism / Science / Science (multidisciplinary) / Single-Cell Gene Expression Analysis / Species Specificity / Transcriptome / Transcriptomes
• ISBN: 9780011636627, 0011636629