The evolution of gene regulation in mammalian cerebellum development

• 成果类型: Article
• 署名作者: Sarropoulos, Ioannis; Sepp, Mari; Yamada, Tetsuya; Schafer, Philipp S. L.; Trost, Nils; Schmidt, Julia; Schneider, Celine; Drummer, Charis; Missbach, Sophie; Taskiran, Ibrahim I.; Hecker, Nikolai; Bravo Gonzalez-Blas, Carmen; Fromel, Robert; Joshi, Piyush; Leushkin, Evgeny; Arnskotter, Frederik; Leiss, Kevin; Okonechnikov, Konstantin; Lisgo, Steven; Palkovits, Miklos; Paabo, Svante; Cardoso-Moreira, Margarida; Kutscher, Lena M.; Behr, Rudiger; Pfister, Stefan M.; Aerts, Stein; Kaessmann, Henrik
• 署名单位: Ruprecht Karls University Heidelberg; Helmholtz Association; German Cancer Research Center (DKFZ); Leibniz Association; Deutsches Primatenzentrum (DPZ); Flanders Institute for Biotechnology (VIB); KU Leuven; Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Helmholtz Association; German Cancer Research Center (DKFZ); Newcastle University - UK; Semmelweis University; Max Planck Society; Okinawa Institute of Science & Technology Graduate University; Francis Crick Institute; Ruprecht Karls University Heidelberg; Ruprecht Karls University Heidelberg; Helmholtz Association; National Center for Tumor Diseases; German Cancer Research Center (DKFZ); Wellcome Trust Sanger Institute; University of Cambridge; University of Cambridge; University of Tartu
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adw9154
• 发表日期: 2026-01-29
• 页码: eadw9154
• 关键词: rna-seq; ultraconserved elements; CELL-DEVELOPMENT; r package; transcription; genome; expression; mouse; landscapes; enhancers

摘要

Gene regulatory changes are considered major drivers of evolutionary innovations, including the cerebellum's expansion during human evolution, yet they remain largely unexplored. In this study, we combined single-nucleus measurements of gene expression and chromatin accessibility from six mammals (human, bonobo, macaque, marmoset, mouse, and opossum) to uncover conserved and diverged regulatory networks in cerebellum development. We identified core regulators of cell identity and developed sequence-based models that revealed conserved regulatory codes. By predicting chromatin accessibility across 240 mammalian species, we reconstructed the evolutionary histories of human cis-regulatory elements, identifying sets associated with positive selection and gene expression changes, including the recent gain of THRB expression in cerebellar progenitor cells. Collectively, our work reveals the shared and mammalian lineage-specific regulatory programs governing cerebellum development.