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Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids [RNA-seq]

ABSTRACT: Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids [RNA-seq]

PROVIDER: PRJNA739740 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14873300_1.fastq.gz	Fastqsanger.gz
	SRR14873300_2.fastq.gz	Fastqsanger.gz
	SRR14873301_1.fastq.gz	Fastqsanger.gz
	SRR14873301_2.fastq.gz	Fastqsanger.gz
	SRR14873302_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

2022-08-24 | GSE178628 | GEO

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

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

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

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

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

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

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

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

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Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids [RNA-seq]

2022-08-24 | GSE178624 | GEO

Hypoxia induces a transcriptional primitive streak signature in ES cells and enhances lineage patterning in gastruloids

Project description:The cellular microenvironment shapes stem cell identity and differentiation capacity. Mammalian early embryos are exposed to hypoxia in vivo and benefit from hypoxic culture in vitro. Yet, how different components of the hypoxia response impact stem cell transcriptional networks and lineage choices remains unclear. Here we investigated the effect of acute and prolonged hypoxia on stem cell states and differentiation efficiencies of embryonic and extraembryonic cells. We show that prolonged hypoxia enhances differentiation of embryonic stem (ES) cells towards the mesendoderm lineage by transcriptionally priming cells with a primitive streak signature including Wnt3 and T expression. Exposure to hypoxia in ES culture or during formation of gastrulation-mimicking organoids (gastruloids) moderates T expression and enhances structural complexity. Hypoxic gastruloids generated without exogenous Wnt induction can spontaneously elongate and self-organize. Direct gene regulation by Hif1a, combined with DNA demethylation and metabolic rewiring modulate the transcriptional response and phenotypic outcome. Our findings highlight the influence of the microenvironment on stem cell function and provide a rationale supportive of applying physiological conditions in synthetic embryo models.

2022-09-05 | PXD026641 | Pride

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

Project description: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.

| S-EPMC9578691 | biostudies-literature

Expression Profile of Chicken Primitive Streak (HH4) Tissues

Project description:In birds and mammals, all mesoderm cells are generated from the primitive streak. Nascent mesoderm cells contain unique dorso-ventral (D/V) identities depending on their relative ingression position along the streak. Molecular mechanisms controlling this initial phase of mesoderm diversification are not well-understood. Using chick model, we generated high-quality transcriptomic datasets of different streak regions and analyzed their molecular heterogeneity.

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