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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
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Does the Aryl Hydrocarbon Receptor Regulate Pluripotency?

Chia-I Ko1, Alvaro Puga1

  • 1Department of Environmental Health and Center for Environmental Genetics University of Cincinnati College of Medicine 160 Panzeca Way, Cincinnati, Ohio, 45267, USA.

Current Opinion in Toxicology
|September 19, 2017
PubMed
Summary
This summary is machine-generated.

The aryl hydrocarbon receptor (AHR) regulates embryonic development by controlling cell pluripotency. Environmental toxicants activating AHR may disrupt this crucial developmental process.

Keywords:
Aryl hydrocarbon receptorcell cycle regulationcell fate decisionsembryonic developmentepigenetic reprogrammingpluripotency

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Area of Science:

  • Developmental Biology
  • Stem Cell Biology
  • Toxicology

Background:

  • Pluripotency is essential for early embryonic development, enabling cells to differentiate into various cell types.
  • The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor known for its role in xenobiotic metabolism and cellular signaling.
  • Emerging evidence suggests AHR's involvement in regulating fundamental cellular processes beyond its canonical functions.

Purpose of the Study:

  • To review the novel role of the aryl hydrocarbon receptor (AHR) in modulating pluripotency during embryonic development.
  • To explore the potential detrimental effects of environmental AHR ligand exposure on developmental processes.
  • To highlight AHR's function as a regulator of cell fate decisions in the early embryo.

Main Methods:

  • Analysis of temporal expression patterns of AHR during embryonic development.
  • Investigation of AHR's repressive effects on key pluripotency factors OCT4 and NANOG.
  • Examination of global DNA methylation changes in relation to AHR expression.
  • Assessment of developmental outcomes in Ahr-null mouse models.

Main Results:

  • AHR expression upregulation correlates with the onset of cell differentiation, indicating its role in cell fate determination.
  • AHR actively represses OCT4 and NANOG, contributing to the exit from pluripotency.
  • AHR expression patterns parallel global DNA methylation changes during development, suggesting a role in chromatin regulation.
  • Ahr-null mice exhibit developmental aberrations due to disrupted pluripotency in inner cell mass cells.

Conclusions:

  • The aryl hydrocarbon receptor (AHR) is a critical regulator of pluripotency, thereby controlling embryonic development.
  • Environmental exposure to AHR ligands may disrupt embryonic development by interfering with pluripotency mechanisms.
  • Understanding AHR's role in development is crucial for assessing the impact of environmental toxicants on reproductive health.