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Eomesodermin dependence delineates the formation of spatially and functionally diverse extra-embryonic hematovascular tissues [scRNA-seq: chimera]

ABSTRACT: Eomesodermin dependence delineates the formation of spatially and functionally diverse extra-embryonic hematovascular tissues [scRNA-seq: chimera]

PROVIDER: PRJNA1145339 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30161358.fastq.gz	Fastqsanger.gz
	SRR30161359.fastq.gz	Fastqsanger.gz
	SRR30161360.fastq.gz	Fastqsanger.gz
	SRR30161361.fastq.gz	Fastqsanger.gz
	SRR30161362.fastq.gz	Fastqsanger.gz

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Eomesodermin dependence delineates the formation of spatially and functionally diverse extra-embryonic hematovascular tissues [Multiome]

Project description:Eomesodermin dependence delineates the formation of spatially and functionally diverse extra-embryonic hematovascular tissues [Multiome]

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Eomesodermin dependence delineates the formation of spatially and functionally diverse extra-embryonic hematovascular tissues [scRNA-seq: chimera]

Project description:During mouse gastrulation, extraembryonic mesoderm (ExEM) contributes to the extraembryonic yolk sac (YS) and allantois, both of which are essential for successful gestation. Although the genetic networks coordinating intra-embryonic mesodermal subtype specification are well-studied, the mechanisms driving ExEM diversification are poorly understood. Here, we reveal that embryoid body (EB) in vitro differentiation generates two distinct lineages of mesodermal cells matching YS and allantois respectively. Combining in vitro models with in vivo chimeric embryo analysis, we discover that Eomesodermin (Eomes) regulates the formation of a subset of YS-fated ExEM but is dispensable for allantois formation. Furthermore, simultaneous disruption of Eomes and T impedes the specification of any YS or allantois mesoderm, indicating compensatory roles for T during allantois formation when Eomes is disrupted. Our study highlights previously unrecognized functional and mechanistic diversity in ExEM diversification and endothelial development and introduces a tractable EB model to dissect the signaling pathways and transcriptional networks driving the formation of key extraembryonic tissues.

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Derivation and characterization of chimera-competent eXtra-Embryonic eNdoderm (XEN) cells from pig blastocysts

Project description:We report for the first time, the derivation and characterization of extra-embryonic endoderm (XEN) cells from primitive endoderm (PrE) of porcine (p) embryos. The pXEN cells can be reliably and reproducibly generated from parthenogenic, in vitro or in vivo derived embryos, and express canonical PrE or XEN cell genes (GATA4, GATA6, SOX17, SALL4, FOXA2, and HNF4A). Transcriptome analysis of pXEN cells revealed close resemblance to yolk sac than any other embryonic or extraembryonic tissue. When introduced into blastocyst stage embryo, the pXEN cells contributed to wide-spread chimerism including visceral yolk sac, chorion, as well as embryonic gut and liver primordium in the fetus. The pXEN cells were shown to be an efficient nuclear donor for generating cloned offspring. Taken together, pXEN cells fulfil a longstanding need for a stable, chimera-competent, and nuclear transfer-compatible porcine embryonic cells with applications for genome editing in livestock.

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Pluripotency Factors Regulate Definitive Endoderm Specification through Eomesodermin

Project description:Understanding the molecular mechanisms controlling early cell fate decisions in mammals is a major objective towards the development of robust methods for the differentiation of human pluripotent stem cells into clinically relevant cell types. Here, we used human embryonic stem cells (hESCs) to study specification of definitive endoderm in vitro. Using a combination of whole genome expression and ChIP-seq analyses, we established a hierarchy of transcription factors regulating endoderm specification. Importantly, pluripotency factors, namely NANOG, OCT4 and SOX2 have an essential function in this network by actively directing differentiation. Indeed, these transcription factors control the expression of EOMES, which marks the onset of endoderm specification. In turn, EOMES interacts with SMAD2/3 to initiate the transcriptional network governing endoderm formation. Together, these results provide for the first time a comprehensive molecular model connecting the transition from pluripotency to endoderm specification during mammalian development. ChIP-Seq of Eomesodermin binding in human embyonic stem cells, differentiated towards an endodermal fate for 48h in chemically-defined culture media. Includes an input DNA control. Supplementary file GSE26097_README.txt contains descriptions of the raw data files and processed data files.

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