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Using human pluripotent stem cells to dissect the molecular basis of human pharyngeal endoderm development [ATAC-seq]

ABSTRACT: Using human pluripotent stem cells to dissect the molecular basis of human pharyngeal endoderm development [ATAC-seq]

PROVIDER: PRJNA922104 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23024203_1.fastq.gz	Fastqsanger.gz
	SRR23024203_2.fastq.gz	Fastqsanger.gz
	SRR23024204_1.fastq.gz	Fastqsanger.gz
	SRR23024204_2.fastq.gz	Fastqsanger.gz
	SRR23024205_1.fastq.gz	Fastqsanger.gz

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Project description:Developmental defects affecting the pharynx and derived tissues can be found in a variety of syndromes, including DiGeorge, 22q11 deletion, CHARGE and Otofaciocervical syndromes. The associated malformations and dysfunctions of pharynx-derived tissues precipitate phenotypes ranging from malformed features and endocrine disorders to severe immunodeficiency, some of which are associated with high morbidity or elaborate treatment and health care costs. While some of the developmental defects have been linked to mutations or single-nucleotide polymorphisms in transcription factors (TFs) or cis-regulatory elements (CREs), the origin of most pharynx-specific birth defects remain poorly understood and the underlying genetic causes as well as epigenetic context remain elusive. Unfortunately, restricted human tissue access, and discordance of genetic factor requirement and phenotypic penetrance of disease associated human mutations when modeled in mice, has prohibited detailed insights on the molecular basis of mentioned human diseases. Human pluripotent stem cells (hPSCs) could in principle allow for detailed a genetically tractable model to decipher the molecular logic of normal and impaired pharynx development. To unlock hPSC for investigation of pharyngeal malformations and ensuing syndromes, we have developed a differentiation protocol to generate human pharyngeal endoderm in vitro. We have applied multi-omic approaches to characterize the molecular logic of cell fate transitions and developed models of gene regulatory network activities.

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