Cellular development and evolution of the mammalian cerebellum

作者全名："Sepp, Mari; Leiss, Kevin; Murat, Florent; Okonechnikov, Konstantin; Joshi, Piyush; Leushkin, Evgeny; Spaenig, Lisa; Mbengue, Noe; Schneider, Celine; Schmidt, Julia; Trost, Nils; Schauer, Maria; Khaitovich, Philipp; Lisgo, Steven; Palkovits, Miklos; Giere, Peter; Kutscher, Lena M.; Anders, Simon; Cardoso-Moreira, Margarida; Sarropoulos, Ioannis; Pfister, Stefan M.; Kaessmann, Henrik"

作者地址："[Sepp, Mari; Leiss, Kevin; Murat, Florent; Leushkin, Evgeny; Mbengue, Noe; Schneider, Celine; Schmidt, Julia; Trost, Nils; Anders, Simon; Sarropoulos, Ioannis; Kaessmann, Henrik] Heidelberg Univ ZMBH, Ctr Mol Biol, DKFZ ZMBH Alliance, Heidelberg, Germany; [Murat, Florent] INRAE, LPGP, Rennes, France; [Okonechnikov, Konstantin; Joshi, Piyush; Spaenig, Lisa; Kutscher, Lena M.; Pfister, Stefan M.] Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany; [Okonechnikov, Konstantin; Joshi, Piyush; Spaenig, Lisa; Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany; [Okonechnikov, Konstantin; Joshi, Piyush; Spaenig, Lisa; Kutscher, Lena M.; Pfister, Stefan M.] German Canc Consortium DKTK, Heidelberg, Germany; [Joshi, Piyush; Spaenig, Lisa; Kutscher, Lena M.] German Canc Res Ctr, Dev Origins Pediat Canc Jr Grp, Heidelberg, Germany; [Schauer, Maria; Giere, Peter] Museum Nat Kunde Berlin, Leibniz Inst Evolut & Biodivers Sci, Berlin, Germany; [Khaitovich, Philipp] Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing, Peoples R China; [Lisgo, Steven] Newcastle Univ, Biosci Inst, Newcastle, England; [Palkovits, Miklos] Semmelweis Univ, Human Brain Tissue Bank, Budapest, Hungary; [Anders, Simon] Heidelberg Univ, BioQuant, Heidelberg, Germany; [Cardoso-Moreira, Margarida] Francis Crick Inst, Evolutionary Dev Biol Lab, London, England; [Pfister, Stefan M.] Heidelberg Univ Hosp, Dept Pediat Hematol & Oncol, Heidelberg, Germany; [Pfister, Stefan M.] Natl Ctr Tumor Dis NCT, Heidelberg, Germany; [Pfister, Stefan M.] Wellcome Sanger Inst, Cambridge, England"

通信作者："Sepp, M; Leiss, K; Sarropoulos, I; Kaessmann, H (通讯作者)，Heidelberg Univ ZMBH, Ctr Mol Biol, DKFZ ZMBH Alliance, Heidelberg, Germany.; Pfister, SM (通讯作者)，Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany.; Pfister, SM (通讯作者)，German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany.; Pfister, SM (通讯作者)，German Canc Consortium DKTK, Heidelberg, Germany.; Pfister, SM (通讯作者)，Heidelberg Univ Hosp, Dept Pediat Hematol & Oncol, Heidelberg, Germany.; Pfister, SM (通讯作者)，Natl Ctr Tumor Dis NCT, Heidelberg, Germany.; Pfister, SM (通讯作者)，Wellcome Sanger Inst, Cambridge, England."

来源：NATURE

ESI学科分类：Multidisciplinary

WOS号：WOS:001163662900020

JCR分区：Q1

影响因子：64.8

年份：2024

卷号：625

期号：7996

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："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 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."

基金机构："Joint MRC/Wellcome [MR/R006237/1]; Joint MRC/Wellcome Trust Human Developmental Biology Resource [MR/R006237/1, MR/X008304/1, 226202/Z/22/Z]; Boehringer Ingelheim Foundation; State of Baden-Wurttemberg through bwHPC; German Research Foundation [INST 35/1134-1 FUGG]; Hungarian Brain Research Program [2017-1.2.1-NKP-2017-00002]; Francis Crick Institute; Cancer Research UK [FC011171]; UK Medical Research Council [FC011171]; Wellcome Trust [FC011171]; European Research Council (ERC) under the European Union [101019268, 819894, 615253]; European Research Council (ERC) [101019268, 819894] Funding Source: European Research Council (ERC)"

基金资助正文："The authors thank C. Conrad, A. Fallahshahroudi, F. Lamanna, D. Kawauchi, T. Trefzer, T. Yamada-Saito, X. Yuan and members of the Kaessmann group for discussions; M. Langlotz, T. Bruening, K. Moe ss inger, E. Renner, M. Toronyay-Kasztner, T. Nath Varma, B. Crespo Lopez, A. Billepp, P. Grimm and T. Wedig for assistance; J. L. VandeBerg for providing archived opossum samples; and the Joint MRC/Wellcome (MR/R006237/1) Human Developmental Biology Resource, Maryland Brain Collection at the Maryland Psychiatric Research Center (NIH NeuroBioBank), Chinese Brain Bank Center, and Human Brain Tissue Bank at Semmelweis University for providing human samples. The human histology images were provided by the Joint MRC/Wellcome Trust (MR/R006237/1, MR/X008304/1 and 226202/Z/22/Z) Human Developmental Biology Resource (www.hdbr.org). We acknowledge the access and services provided by the Imaging Centre at the European Molecular Biology Laboratory (EMBL IC), generously supported by the Boehringer Ingelheim Foundation. Purchase of the NextSeq 550 instrument was supported by the Klaus Tschira Foundation. The computational cluster bwForCluster of the Heidelberg University Computational Center is supported by the State of Baden-Wurttemberg through bwHPC and the German Research Foundation (INST 35/1134-1 FUGG). M.P. was supported by a grant from the Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002). M.C.-M. was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC011171), the UK Medical Research Council (FC011171), and the Wellcome Trust (FC011171). This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (VerteBrain to H.K., grant agreement no. 101019268; BRAIN-MATCH to S.M.P., grant agreement no. 819894), and Seventh Framework Programme (FP7-2007-2013) (OntoTransEvol to H.K., grant agreement no. 615253)."