The evolution of gene regulation in mammalian cerebellum development [Research Data]

DOI

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.

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Processed data and DeepCeREvo’s predictions can be interactively explored or downloaded at https://apps.kaessmannlab.org/cerebellum_genreg_evodevo_app.

Identifier
DOI https://doi.org/10.11588/DATA/GDSZG9
Related Identifier IsSupplementTo https://doi.org/10.1101/2025.03.14.643248
Metadata Access https://heidata.uni-heidelberg.de/oai?verb=GetRecord&metadataPrefix=oai_datacite&identifier=doi:10.11588/DATA/GDSZG9
Provenance
Creator Sarropoulos, Ioannis ORCID logo; Sepp, Mari ORCID logo; Yamada, Tetsuya (ORCID: 0000-0001-8601-737X); Schäfer, Philipp S. L. ORCID logo; Trost, Nils (ORCID: 0000-0002-5171-018X); Schmidt, Julia; Schneider, Céline; Drummer, Charis; Mißbach, Sophie; Taskiran, Ibrahim I. ORCID logo; Hecker, Nikolai ORCID logo; González-Blas, Carmen Bravo ORCID logo; Frömel, Robert ORCID logo; Joshi, Piyush (ORCID: 0000-0002-5631-336X); Leushkin, Evgeny ORCID logo; Arnskötter, Frederik ORCID logo; Leiss, Kevin ORCID logo; Okonechnikov, Konstantin ORCID logo; Lisgo, Steven ORCID logo; Palkovits, Miklós ORCID logo; Pääbo, Svante; Cardoso-Moreira, Margarida ORCID logo; Kutscher, Lena M. ORCID logo; Behr, Rüdiger; Pfister, Stefan M. ORCID logo; Aerts, Stein ORCID logo; Kaessmann, Henrik (ORCID: 0000-0001-7563-839X)
Publisher heiDATA
Contributor Sarropoulos, Ioannis; Sepp, Mari; Yamada, Tetsuya; Kaessmann, Henrik
Publication Year 2025
Funding Reference European Research Council (ERC) VerteBrain, grant agreement no. 101019268 ; European Research Council (ERC) BRAIN-MATCH, grant agreement no. 819894 ; European Research Council (ERC) OntoTransEvol, grant agreement no. 615253
Rights CC BY 4.0; info:eu-repo/semantics/openAccess; http://creativecommons.org/licenses/by/4.0
OpenAccess true
Contact Sarropoulos, Ioannis (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)); Sepp, Mari (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)); Yamada, Tetsuya (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH)); Kaessmann, Henrik (Heidelberg University, Center for Molecular Biology of Heidelberg University (ZMBH))
Representation
Resource Type Dataset
Format application/x-tar
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Version 1.0
Discipline Biology; Life Sciences; Medicine