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The primitive endoderm supports lineage plasticity to enable regulative development [CUT&Tag H3K4me3]

ABSTRACT: The primitive endoderm supports lineage plasticity to enable regulative development [CUT&Tag H3K4me3]

PROVIDER: PRJNA1110234 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28995236.fastq.gz	Fastqsanger.gz
	SRR28995237.fastq.gz	Fastqsanger.gz
	SRR28995238.fastq.gz	Fastqsanger.gz
	SRR28995239.fastq.gz	Fastqsanger.gz
	SRR28995240.fastq.gz	Fastqsanger.gz

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Project description:Mammalian blastocyst formation involves the sequential specification of trophectoderm and the differentiation of inner cell mass into either epiblast or primitive endoderm. During this time, the embryo maintains a window of plasticity and able to redirect its cellular fate when challenged experimentally. In this context, we found that the primitive endoderm alone was capable of regenerating a complete blastocyst and continue normal postimplantation development. We identify an in vitro population similar to the early primitive endoderm in vivo that exhibits plasticity, forms three dimensional embryoid structures and exhibits multilineage competence in chimera assays. Here, we find OCT4 as the main player in collaborating with endodermal transcription factors to maintain pluripotent enhancers in a state that is primed for activation mediated by JAK/STAT signalling. Our observations support the notion that transcription factor persistence underlies plasticity in regulative development and highlights the importance of primitive endoderm in perturbed development.

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Project description:Mammalian blastocyst formation involves the specification of trophectoderm followed by differentiation of the inner cell mass into embryonic epiblast and extra-embryonic primitive endoderm (PrE). During this time, the embryo maintains a window of plasticity and can redirect its cellular fate when challenged experimentally. In this context, we found that the PrE alone was sufficient to regenerate a complete blastocyst and continue postimplantation development. We identify an in vitro population similar to the early PrE in vivo that exhibits the same embryonic and extra-embryonic potency and can form complete stem cell-based embryo models termed blastoids. Commitment in the PrE is suppressed by JAK/STAT signalling, collaborating with OCT4 and the sustained expression of a subset of pluripotency-related transcription factors that safeguard an enhancer landscape permissive for multi-lineage differentiation. Our observations support the notion that transcription factor persistence underlies plasticity in regulative development and highlights the importance of the PrE in perturbed development.

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Project description:Mammalian blastocyst formation involves the specification of the trophectoderm followed by the differentiation of the inner cell mass into embryonic epiblast and extra-embryonic primitive endoderm (PrE). During this time, the embryo maintains a window of plasticity and can redirect its cellular fate when challenged experimentally. In this context, we found that the PrE alone was sufficient to regenerate a complete blastocyst and continue post-implantation development. We identify an in vitro population similar to the early PrE in vivo that exhibits the same embryonic and extra-embryonic potency and can form complete stem cell-based embryo models, termed blastoids. Commitment in the PrE is suppressed by JAK/STAT signaling, collaborating with OCT4 and the sustained expression of a subset of pluripotency-related transcription factors that safeguard an enhancer landscape permissive for multi-lineage differentiation. Our observations support the notion that transcription factor persistence underlies plasticity in regulative development and highlight the importance of the PrE in perturbed development.

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The primitive endoderm supports lineage plasticity to enable regulative development

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