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Lookup NU author(s): Dr Steven LisgoORCiD
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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.
Author(s): Sarropoulos I, Sepp M, Yamada T, Schafer PSL, Trost N, Schmidt J, Schneider C, Drummer C, Missbach S, Taskiran II, Hecker N, Bravo Gonzalez-Blas C, Fromel R, Joshi P, Leushkin E, Arnskotter F, Leiss K, Okonechnikov K, Lisgo S, Palkovits M, Paabo S, Cardoso-Moreira M, Kutscher LM, Behr R, Pfister SM, Aerts S, Kaessmann H
Publication type: Article
Publication status: Published
Journal: Science
Year: 2026
Volume: 391
Issue: 6784
Print publication date: 29/01/2026
Online publication date: 29/01/2026
Acceptance date: 25/10/2025
ISSN (print): 0036-8075
ISSN (electronic): 1095-9203
Publisher: American Association for the Advancement of Science
URL: https://doi.org/10.1126/science.adw9154
DOI: 10.1126/science.adw9154
PubMed id: 41610256
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