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TET activity safeguards pluripotency throughout embryonic dormancy

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Stötzel,  Maximilian       
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Cheng,  Chieh-Yu       
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Ilik,  Ibrahim A.       
Quantitative RNA Biology (Tugce Aktas), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Sampath Kumar,  Abhishek       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Akbari-Omgba,  Persia       
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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van der Weijden,  Vera A.       
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zhang,  Yufei
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Vingron,  Martin       
Transcriptional Regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Meissner,  Alexander       
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Aktas,  Tugce       
Quantitative RNA Biology (Tugce Aktas), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Kretzmer,  Helene       
Computational Genomics (Helene Kretzmer), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Bulut-Karslioglu,  Aydan       
Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

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s41594-024-01313-7.pdf
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Citation

Stötzel, M., Cheng, C.-Y., Ilik, I. A., Sampath Kumar, A., Akbari-Omgba, P., van der Weijden, V. A., et al. (2024). TET activity safeguards pluripotency throughout embryonic dormancy. Nature Structural & Molecular Biology. doi:10.1038/s41594-024-01313-7.


Cite as: https://hdl.handle.net/21.11116/0000-000F-6A03-7
Abstract
Dormancy is an essential biological process for the propagation of many life forms through generations and stressful conditions. Early embryos of many mammals are preservable for weeks to months within the uterus in a dormant state called diapause, which can be induced in vitro through mTOR inhibition. Cellular strategies that safeguard original cell identity within the silent genomic landscape of dormancy are not known. Here we show that the protection of cis-regulatory elements from silencing is key to maintaining pluripotency in the dormant state. We reveal a TET-transcription factor axis, in which TET-mediated DNA demethylation and recruitment of methylation-sensitive transcription factor TFE3 drive transcriptionally inert chromatin adaptations during dormancy transition. Perturbation of TET activity compromises pluripotency and survival of mouse embryos under dormancy, whereas its enhancement improves survival rates. Our results reveal an essential mechanism for propagating the cellular identity of dormant cells, with implications for regeneration and disease.