Cellular development and evolution of the mammalian cerebellum
Cellular development and evolution of the mammalian cerebellum
The expansion of the neocortex, one of the hallmarks of mammalian evolution1,2, was accompanied by an increase in the number of cerebellar neurons3. 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 the development of the cerebellum from early neurogenesis to adulthood in human, mouse, and the marsupial opossum. Our cross-species analyses revealed that the cellular composition and differentiation dynamics throughout cerebellum development are largely conserved, except for human Purkinje cells. Global transcriptome profiles, conserved cell state markers, and gene expression trajectories across neuronal differentiation show that the cerebellar cell type-defining programs have been overall preserved for at least 160 million years. However, we also discovered differences. We identified 3,586 genes that either gained or lost expression in cerebellar cells in one of the species, and 541 genes that evolved new expression trajectories during neuronal differentiation. The potential functional relevance of these cross-species differences is highlighted by the diverged expression patterns of several human disease-associated genes. Altogether, our study reveals shared and lineage-specific programs governing the cellular development of the mammalian cerebellum, and expands our understanding of the evolution of mammalian organ development.
Lisgo Steven、Sp?nig Lisa、Leiss Kevin、Sarropoulos Ioannis、Murat Florent、Leushkin Evgeny、Mbengue Noe、Kutscher Lena M.、Trost Nils、Anders Simon、Schmidt Julia、Sepp Mari、Kaessmann Henrik、Cardoso-Moreira Margarida、Palkovits Mikl¨?s、Pfister Stefan M.、Giere Peter、Okonechnikov Konstantin、Schneider C¨|line、Joshi Piyush、Khaitovich Philipp
Biosciences Institute, Newcastle UniversityHopp-Children?ˉs Cancer Center Heidelberg (KiTZ)||Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)||Developmental Origins of Pediatric Cancer Junior Group, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceHopp-Children?ˉs Cancer Center Heidelberg (KiTZ)||Developmental Origins of Pediatric Cancer Junior Group, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance||BioQuant, Heidelberg UniversityCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceCenter for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceEvolutionary Developmental Biology Laboratory, Francis Crick InstituteHuman Brain Tissue Bank, Semmelweis UniversityHopp-Children?ˉs Cancer Center Heidelberg (KiTZ)||Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)||Department of Pediatric Hematology and Oncology, Heidelberg University HospitalMuseum f¨1r Naturkunde Berlin, Leibniz Institute for Research on Evolution and Biodiversity Science at the Humboldt University BerlinHopp-Children?ˉs Cancer Center Heidelberg (KiTZ)||Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH AllianceHopp-Children?ˉs Cancer Center Heidelberg (KiTZ)||Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)||Developmental Origins of Pediatric Cancer Junior Group, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK)Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology
细胞生物学遗传学分子生物学
Lisgo Steven,Sp?nig Lisa,Leiss Kevin,Sarropoulos Ioannis,Murat Florent,Leushkin Evgeny,Mbengue Noe,Kutscher Lena M.,Trost Nils,Anders Simon,Schmidt Julia,Sepp Mari,Kaessmann Henrik,Cardoso-Moreira Margarida,Palkovits Mikl¨?s,Pfister Stefan M.,Giere Peter,Okonechnikov Konstantin,Schneider C¨|line,Joshi Piyush,Khaitovich Philipp.Cellular development and evolution of the mammalian cerebellum[EB/OL].(2025-03-28)[2025-08-03].https://www.biorxiv.org/content/10.1101/2021.12.20.473443.点此复制
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