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Embryonic Stem Cells00:58

Embryonic Stem Cells

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Embryonic stem (ES) cells are undifferentiated pluripotent cells, meaning they can produce any cell type in the body. This gives them tremendous potential in science and medicine since they can generate specific cell types for use in research or to replace body cells lost due to damage or disease.
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Embryonic stem (ES) cells were first discovered in mice in 1981 by Martin Evans. In 1998, James Thomson identified a method to isolate embryonic stem cells from humans. Human embryonic stem cells (hESCs) are obtained from 3-5 day old embryos that remain unused after an in vitro fertilization procedure.
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Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
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Combined DNA-RNA Fluorescent In situ Hybridization FISH to Study X Chromosome Inactivation in Differentiated Female Mouse Embryonic Stem Cells
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Silver Nanoparticles Compromise Female Embryonic Stem Cell Differentiation through Disturbing X Chromosome

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  • 1State Key Laboratory of Environmental Chemistry and Ecotoxicology , Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , Beijing 100085 , China.

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Low-dose silver nanoparticles disrupt X chromosome inactivation in female stem cells, hindering differentiation without causing cell death. This finding reveals a novel mechanism of developmental toxicity beyond oxidative stress.

Keywords:
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Area of Science:

  • Nanotechnology
  • Developmental Biology
  • Toxicology

Background:

  • Widespread use of silver nanoparticles (AgNPs) poses health risks.
  • Limited understanding of AgNP effects on early development and low-dose toxicity.
  • Previous studies primarily attributed AgNP toxicity to oxidative stress.

Purpose of the Study:

  • Investigate the mechanism of AgNP toxicity in female mouse embryonic stem cells (mESCs) at low doses.
  • Explore effects beyond oxidative stress, focusing on X chromosome inactivation (XCI).
  • Determine if AgNPs impact differentiation and gene expression in mESCs.

Main Methods:

  • Exposure of female mESCs to low-dose AgNPs.
  • Assessment of cytotoxicity and differentiation.
  • Analysis of X chromosome inactivation (XCI) dynamics (Xa and Xi maintenance).
  • Evaluation of X-linked gene expression and histone modifications (H3K27me3).
  • Comparison with male mESCs.

Main Results:

  • Low-dose AgNPs caused significant differentiation retardation in female mESCs without observable cytotoxicity.
  • AgNPs disordered XCI, leading to expedited inactivation of the inactive X chromosome (Xi) and weakened maintenance of the active X chromosome (Xa).
  • Repression of key X-linked differentiation genes was observed, linked to increased H3K27me3 enrichment.
  • Male mESCs showed no differentiation impairment under similar AgNP exposure.

Conclusions:

  • AgNPs at low concentrations compromise female mESC differentiation by disrupting XCI.
  • This study uncovers a novel mechanism of AgNP developmental toxicity.
  • The findings provide a model for studying AgNP-induced developmental toxicity, particularly concerning XCI disruption.