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Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids

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López-Anguita,  Natalia       
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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Gassaloglu,  Seher Ipek
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society;

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

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Typou,  Marina
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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Buschow,  Rene       
Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Veenvliet,  Jesse V.
Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), 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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Development_López-Anguita_2022.pdf
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Citation

López-Anguita, N., Gassaloglu, S. I., Stötzel, M., Bolondi, A., Conkar, D., Typou, M., et al. (2022). Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids. Development, 149(20): dev200679. doi:10.1242/dev.200679.


Cite as: https://hdl.handle.net/21.11116/0000-0009-0871-F
Abstract
The cellular microenvironment, together with intrinsic regulators, shapes stem cell identity and differentiation capacity. Mammalian early embryos are exposed to hypoxia in vivo and appear to benefit from hypoxic culture in vitro. Yet, how hypoxia influences stem cell transcriptional networks and lineage choices remain poorly understood. Here, we investigated the molecular effects of acute and prolonged hypoxia on embryonic and extra-embryonic stem cells as well as the functional impact on differentiation potential. We find a temporal and cell type-specific transcriptional response including an early primitive streak signature in hypoxic embryonic stem cells mediated by HIF1α. Using a 3D gastruloid differentiation model, we show that hypoxia-induced T expression enables symmetry breaking and axial elongation in the absence of exogenous WNT activation. When combined with exogenous WNT activation, hypoxia enhances lineage representation in gastruloids, as demonstrated by highly enriched signatures of gut endoderm, notochord, neuromesodermal progenitors and somites. Our findings directly link the microenvironment to stem cell function and provide a rationale supportive of applying physiological conditions in models of embryo development.