|
| 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
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
|
| 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.
|
| |
|
| Overall design |
Refer to individual Series
|
| |
|
| Citation(s) |
36102628 |
| |
| Submission date |
Jun 21, 2021 |
| Last update date |
Nov 17, 2022 |
| Contact name |
Natalia Lopez-Anguita |
| E-mail(s) |
anguita@molgen.mpg.de
|
| Organization name |
Max Planck Institute for Molecular Genetics
|
| Department |
Genome Regulation
|
| Lab |
Bulut-Karslioglu Lab
|
| Street address |
Ihnestraße 63
|
| City |
Berlin |
| State/province |
Berlin |
| ZIP/Postal code |
14195 |
| Country |
Germany |
| |
|
| Platforms (2) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (27)
|
|
| This SuperSeries is composed of the following SubSeries: |
| GSE178624 |
Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids [RNA-seq] |
| GSE195544 |
Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids |
| GSE195545 |
Hypoxia induces an early primitive streak signature, enhancing spontaneous elongation and lineage representation in gastruloids |
|
| Relations |
| BioProject |
PRJNA739739 |
Less...
More...