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The evolution of gene regulation in mammalian cerebellum development

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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 (h...

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Main Authors: Sarropoulos, Ioannis (Author) , Sepp, Mari (Author) , Yamada, Tetsuya (Author) , Schäfer, Philipp (Author) , Trost, Nils (Author) , Schmidt, Julia (Author) , Schneider, Céline (Author) , Drummer, Charis (Author) , Mißbach, Sophie (Author) , Taskiran, Ibrahim I. (Author) , Hecker, Nikolai (Author) , Bravo González-Blas, Carmen (Author) , Frömel, Robert (Author) , Joshi, Piyush (Author) , Leushkin, Evgeny (Author) , Arnskötter, Carl Frederik (Author) , Leiss, Kevin (Author) , Okonechnikov, Konstantin (Author) , Lisgo, Steven (Author) , Palkovits, Miklós (Author) , Pääbo, Svante (Author) , Cardoso-Moreira, Margarida (Author) , Kutscher, Lena (Author) , Behr, Rüdiger (Author) , Pfister, Stefan (Author) , Aerts, Stein (Author) , Kaessmann, Henrik (Author)
Format: Article (Journal)
Language:English
Published: 29 January 2026
In: Science
Year: 2026, Volume: 391, Issue: 6784, Pages: 1-25
ISSN:1095-9203
DOI:10.1126/science.adw9154
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/science.adw9154
Verlag, lizenzpflichtig, Volltext: https://www.science.org/doi/10.1126/science.adw9154
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Author Notes:Ioannis Sarropoulos, Mari Sepp, Tetsuya Yamada, Philipp S. L. Schäfer, Nils Trost, Julia Schmidt, Céline Schneider, Charis Drummer, Sophie Mißbach, Ibrahim I. Taskiran, Nikolai Hecker, Carmen Bravo González-Blas, Robert Frömel, Piyush Joshi, Evgeny Leushkin, Frederik Arnskötter, Kevin Leiss, Konstantin Okonechnikov, Steven Lisgo, Miklós Palkovits, Svante Pääbo, Margarida Cardoso-Moreira, Lena M. Kutscher, Rüdiger Behr, Stefan M. Pfister, Stein Aerts, Henrik Kaessmann
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Summary: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.
Item Description:Gesehen am 11.05.2026
Physical Description:Online Resource
ISSN:1095-9203
DOI:10.1126/science.adw9154

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