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Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122003 | GEO | 2018/10/31

REPOSITORIES: GEO

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Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells.

Project description:Dioxin and dioxin-related polychlorinated biphenyls are potent toxicants with association with developmental heart defects and congenital heart diseases. However, the underlying mechanism of their developmental toxicity is not fully understood. Further, different animals show distinct susceptibility and phenotypes after exposure, suggesting possible species-specific effects. Using a human embryonic stem cell (ESC) cardiomyocyte differentiation model, we examined the impact, susceptible window, and dosage of 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD) on human cardiac development. We showed that treatment of human ESCs with TCDD at the ESC stage inhibits cardiomyocyte differentiation, and the effect is largely mediated by the aryl hydrocarbon receptor (AHR). We further identified genes that are differentially expressed after TCDD treatment by RNA-sequencing, and genomic regions that are occupied by AHR by chromatin immunoprecipitation and high-throughput sequencing. Our results support the model that TCDD impairs human ESC cardiac differentiation by promoting AHR binding and repression of key mesoderm genes. More importantly, our study demonstrates the toxicity of dioxin in human embryonic development and uncovered a novel mechanism by which dioxin and AHR regulates lineage commitment. It also illustrates the power of ESC-based models in the systematic study of developmental toxicology.

| S-EPMC6547817 | biostudies-literature

Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells (RNA-Seq)

2018-10-31 | GSE122002 | GEO

Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells (ChIP-Seq)

2018-10-31 | GSE122001 | GEO

Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells

Project description:Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells

| PRJNA502994 | ENA

Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells (ChIP-Seq)

Project description:Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells (ChIP-Seq)

| PRJNA502992 | ENA

Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells (RNA-Seq)

Project description:Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells (RNA-Seq)

| PRJNA502997 | ENA

Isolation of highly enriched cardiac mesoderm from differentiating human embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-11-05 | E-GEOD-74713 | biostudies-arrayexpress

CTCF acetylation at lysine 20 is required for early cardiac mesoderm differentiation from embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-24 | GSE181705 | GEO

Isolation of highly enriched cardiac mesoderm from differentiating human embryonic stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-11-05 | GSE74713 | GEO

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