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

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.

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Development_López-Anguita_2022.pdf (Publisher version), 49MB
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 Creators:
López-Anguita, Natalia1, Author                 
Gassaloglu, Seher Ipek2, Author           
Stötzel, Maximilian1, Author                 
Bolondi, Adriano3, Author                 
Conkar , Deniz, Author
Typou, Marina1, Author           
Buschow, Rene4, Author                 
Veenvliet, Jesse V.2, Author           
Bulut-Karslioglu, Aydan1, Author           
Affiliations:
1Stem Cell Chromatin (Aydan Bulut-Karslioglu), Dept. of Genome Regulation, (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014185              
2Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              
3Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
4Microscopy and Cryo-Electron Microscopy (Head: Thorsten Mielke), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479668              

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Free keywords: Hypoxia, Hif1a, WNT, Gastruloid, Pluripotency
 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.

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Language(s): eng - English
 Dates: 2022-08-032022-10
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1242/dev.200679
 Degree: -

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Title: Development
  Other : Development
Source Genre: Journal
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Publ. Info: Cambridge, Cambridgeshire : Company of Biologists
Pages: - Volume / Issue: 149 (20) Sequence Number: dev200679 Start / End Page: - Identifier: ISSN: 0950-1991
CoNE: https://pure.mpg.de/cone/journals/resource/954927546241