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Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids

MPS-Authors
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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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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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Virta,  Iiris
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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Hetzel,  Sara
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50118

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

/persons/resource/persons252563

Maitschke-Rajasekharan,  Ronald
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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Mattei,  Alexandra L.
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50427

Meierhofer,  David
Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons203770

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

/persons/resource/persons204389

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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López-Anguita_2021.pdf
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Citation

López-Anguita, N., Gassaloglu, S. I., Stötzel, M., Typou, M., Virta, I., Hetzel, S., et al. (2021). Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids. BioRxiv. doi:10.1101/2021.07.21.452906.


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, components of the hypoxia response and how their interplay impacts stem cell transcriptional networks and lineage choices remain poorly understood. Here we investigated the molecular effects of acute and prolonged hypoxia on distinct embryonic and extraembryonic stem cell types 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 (ES) cells. 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. Importantly, hypoxia also modulates T levels in conventional gastruloids and enhances representation of endodermal and neural markers. Mechanistically, we identify Hif1α as a central factor that mediates the transcriptional response to hypoxia in balance with epigenetic and metabolic rewiring. Our findings directly link the microenvironment to stem cell function and provide a rationale supportive of applying physiological conditions in models of embryo development.