Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the differentiation of embryonic stem cells towards pancreatic lineage and pancreatic beta cell function.

08:00 EDT 10th June 2019 | BioPortfolio

Summary of "Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the differentiation of embryonic stem cells towards pancreatic lineage and pancreatic beta cell function."

Animal and epidemiological studies demonstrated association of persistent exposure of TCDD, an endocrine disrupting chemical, to susceptibility of type 2 diabetes (T2D). High doses of TCDD were commonly employed in experimental animals to illustrate its diabetogenic effects. Data linking the epigenetic effects of low doses of TCDD on embryonic cells to T2D susceptibility risks is very limited. To address whether low dose exposure to TCDD would affect pancreatic development, hESCs pretreated with TCDD at concentrations similar to human exposure were differentiated towards pancreatic lineage cells, and their global DNA methylation patterns were determined. Our results showed that TCDD-treated hESCs had impaired pancreatic lineage differentiation potentials and altered global DNA methylation patterns. Four of the hypermethylated genes (PRKAG1, CAPN10, HNF-1B and MAFA) were validated by DNA bisulfite sequencing. PRKAG1, a regulator in the AMPK signaling pathway critical for insulin secretion, was selected for further functional study in the rat insulinoma cell line, INS-1E cells. TCDD treatment induced PRKAG1 hypermethylation in hESCs, and the hypermethylation was maintained after pancreatic progenitor cells differentiation. Transient Prkag1 knockdown in the INS-1E cells elevated glucose stimulated insulin secretions (GSIS), possibly through mTOR signaling pathway. The current study suggested that early embryonic exposure to TCDD might alter pancreatogenesis, increasing the risk of T2D.


Journal Details

This article was published in the following journal.

Name: Environment international
ISSN: 1873-6750
Pages: 104885


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Medical and Biotech [MESH] Definitions

A group of toxic chemical compounds that share chemical structures and biological characteristics that are related to the potent carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The malignant stem cells of TERATOCARCINOMAS, which resemble pluripotent stem cells of the BLASTOCYST INNER CELL MASS. The EC cells can be grown in vitro, and experimentally induced to differentiate. They are used as a model system for studying early embryonic cell differentiation.

A homeodomain protein and transcription regulator that functions in BLASTOCYST INNER CELL MASS and EMBRYONIC STEM CELL proliferation and CELL SELF RENEWAL. It confers pluripotency on embryonic stem cells and prevents their differentiation towards extraembryonic ENDODERM and trophectoderm (TROPHOBLAST) CELL LINEAGES.

A herbicide that contains equal parts of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), as well as traces of the contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.

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