Quantitative Proteomics Study Reveals Changes in the Molecular Landscape of Human Embryonic Stem Cells with Impaired Stem Cell Differentiation upon Exposure to Titanium Dioxide Nanoparticles

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2018-06, Vol.14 (23), p.e1800190-n/a
• Main Authors: Pan, Lei, Lee, Yew Mun, Lim, Teck Kwang, Lin, Qingsong, Xu, Xiuqin
• Format: Article
• Language: English
• Subjects: Biocompatibility; Deoxyribonucleic acid; Differentiation (biology); DNA; embryonic stem cells; Embryos; Exposure; Hazards; Molecular chains; Nanoparticles; Nanotechnology; Proteins; Proteomics; Stem cells; Surgical implants; Titanium; Titanium dioxide; Toxicity
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201800190

The increasing number of nanoparticles (NPs) being used in various industries has led to growing concerns of potential hazards that NP exposure can incur on human health. However, its global effects on humans and the underlying mechanisms are not systemically studied. Human embryonic stem cells (hESCs), with the ability to differentiate to any cell types, provide a unique system to assess cellular, developmental, and functional toxicity in vitro within a single system highly relevant to human physiology. Here, the quantitative proteomics approach is adopted to evaluate the molecular consequences of titanium dioxide NPs (TiO2 NPs) exposure in hESCs. The study identifies ≈328 unique proteins significantly affected by TiO2 NPs exposure. Proteomics analysis highlights that TiO2 NPs can induce DNA damage, elevated oxidative stress, apoptotic responses, and cellular differentiation. Furthermore, in vivo analysis demonstrates remarkable reduction in the ability of hESCs in teratoma formation after TiO2 NPs exposure, suggesting impaired pluripotency. Subsequently, it is found that TiO2 NPs can disrupt hESC mesoderm differentiation into cardiomyocytes. The study unveils comprehensive changes in the molecular landscape of hESCs by TiO2 NPs and identifies the impact which TiO2 NPs can have on the pluripotency and differentiation properties of human stem cells. The global effect of TiO2 nanoparticles (NPs) exposure on human embryonic stem cells (hESCs) is assessed by quantitative proteomics and bioinformatics analysis. Results show that TiO2 NPs can induce cell cycle perturbation, elevated oxidative stress, DNA damage, and apoptotic responses. Furthermore, it is found that TiO2 NPs can impact on the pluripotency of hESCs and disrupt mesoderm differentiation into cardiomyocytes.