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Abnormal neural differentiation in response to graphene quantum dots through histone modification interference.

Tingting Ku1, Zhihua Ren2, Renjun Yang2

  • 1State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, 030006, China.

Environment International
|October 13, 2022
PubMed
Summary

Graphene quantum dots (GQDs) can harm neural development. OH-GQDs disrupt neurogenesis by altering histone modifications, with surface chemistry influencing toxicity.

Keywords:
BMP signaling pathwayEmbryonic stem cellsGraphene quantum dotsHistone modificationNeural differentiation

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Area of Science:

  • Nanomedicine
  • Toxicology
  • Developmental Biology

Background:

  • Graphene quantum dots (GQDs) are increasingly used in biomedicine, raising concerns about their environmental exposure and neurotoxicological impacts.
  • Assessing the nanosafety of GQDs on the nervous system, particularly their effects on neurodevelopment and underlying mechanisms, remains crucial but elusive.

Purpose of the Study:

  • To investigate the neural developmental toxicity of hydroxylated (OH-GQDs) and aminated (NH2-GQDs) graphene quantum dots.
  • To elucidate the molecular mechanisms by which GQDs affect neural differentiation using mouse embryonic stem cells (mESCs).

Main Methods:

  • Utilized mouse embryonic stem cells (mESCs) to model neural development and differentiation.
  • Analyzed the impact of OH-GQDs and NH2-GQDs on ectoderm development, neural precursor formation, and neurogenesis.
  • Investigated molecular mechanisms including histone modification (H3K27me3 enrichment) and signaling pathways (BMP pathway) affecting neural differentiation.

Main Results:

  • OH-GQDs significantly inhibited ectoderm development and reduced neural precursor formation and neurogenesis in differentiating mESCs.
  • The mechanism involved increased H3K27me3 enrichment at the Smad6 promoter, activating a histone modification-mediated BMP signaling pathway that impaired neural differentiation.
  • OH-GQDs induced greater histone modification imbalance and delayed neural differentiation compared to NH2-GQDs, indicating surface functionalization-specific toxicity.

Conclusions:

  • Graphene quantum dots, particularly OH-GQDs, pose risks to neurodevelopment by disrupting key differentiation processes through epigenetic modifications.
  • The surface functionalization of GQDs critically influences their neurodevelopmental toxicity, highlighting the importance of chemical modification in nanosafety assessments.
  • This study provides crucial insights into the adverse neurodevelopmental effects of GQDs and the impact of their chemical structure on bioactivity.