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| Status |
Public on Aug 24, 2022 |
| Title |
Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 extraembryonic 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 (ESCs) mediated by HIF1. 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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| Overall design |
Examination of germ layer representation in coventional gastruloids (+Chi) cultured in normoxia and hypoxia and unconventional gastruloids (-Chi) cultured in hypoxia.
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| Contributor(s) |
Lopez-Anguita N, Gassaloglu SI, Stötzel M, Bolondi A, Conkar D, Typou M, Buschow R, Veenvliet J, Bulut-Karslioglu A |
| Citation(s) |
36102628 |
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| Submission date |
Jan 27, 2022 |
| Last update date |
Nov 17, 2022 |
| Contact name |
Natalia Lopez-Anguita |
| E-mail(s) |
anguita@molgen.mpg.de
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| Organization name |
Max Planck Institute for Molecular Genetics
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| Department |
Genome Regulation
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| Lab |
Bulut-Karslioglu Lab
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| Street address |
Ihnestraße 63
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| City |
Berlin |
| State/province |
Berlin |
| ZIP/Postal code |
14195 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (1) |
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| This SubSeries is part of SuperSeries: |
| GSE178628 |
Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids |
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| Relations |
| BioProject |
PRJNA801224 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE195544_RAW.tar |
34.7 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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