ArticleDevelopment (Cambridge, England)2022
Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids.
Article in Development (Cambridge, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 33 citations in OpenAlex.
- Regeneration programs buffer genetic defects in animal development.PLoS biology · 2026Article
- The notochord: development, disease and stem cell-based modelling.Development (Cambridge, England) · 2026Review
- Organizers in a dish: Modeling human CNS morphogenesis.Developmental cell · 2026Review
- Developmental Hypoxia Enhances Kidney Organoid Complexity and Maturity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Size-dependent temporal decoupling of morphogenesis and transcriptional programs in pseudoembryos.Science advances · 2025Article
- High-altitude hypoxia exposure alters follicular metabolome and oocyte developmental potential in women.Archives of gynecology and obstetrics · 2025Article
- Three-dimensional stem cell models of mammalian gastrulation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- The logic of monsters: development and morphological diversity in stem-cell-based embryo models.Interface focus · 2024Review
- PHD2 safeguards modest mesendoderm development.Communications biology · 2024Article
- Redox heterogeneity in mouse embryonic stem cells individualizes cell fate decisions.Developmental cell · 2024Article
- Haematopoietic development and HSC formation in vitro: promise and limitations of gastruloid models.Emerging topics in life sciences · 2023Review
- Gastruloids - a minimalistic model to study complex developmental metabolism.Emerging topics in life sciences · 2023Review
- Conserved enhancers control notochord expression of vertebrate Brachyury.Nature communications · 2023Article
- Hypoxia-induced cancer cell reprogramming: a review on how cancer stem cells arise.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.