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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

Highly parallelized human embryonic stem cell differentiation to cardiac mesoderm in nanoliter chambers on a microfluidic chip.

Project description:Human stem cell-derived cells and tissues hold considerable potential for applications in regenerative medicine, disease modeling and drug discovery. The generation, culture and differentiation of stem cells in low-volume, automated and parallelized microfluidic chips hold great promise to accelerate the research in this domain. Here, we show that we can differentiate human embryonic stem cells (hESCs) to early cardiac mesodermal cells in microfluidic chambers that have a volume of only 30 nanoliters, using discontinuous medium perfusion. 64 of these chambers were parallelized on a chip which contained integrated valves to spatiotemporally isolate the chambers and automate cell culture medium exchanges. To confirm cell pluripotency, we tracked hESC proliferation and immunostained the cells for pluripotency markers SOX2 and OCT3/4. During differentiation, we investigated the effect of different medium perfusion frequencies on cell reorganization and the expression of the early cardiac mesoderm reporter MESP1mCherry by live-cell imaging. Our study demonstrates that microfluidic technology can be used to automatically culture, differentiate and study hESC in very low-volume culture chambers even without continuous medium perfusion. This result is an important step towards further automation and parallelization in stem cell technology.

| S-EPMC8166733 | biostudies-literature

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