Single-cell transcriptomics uncovers the impacts of titanium dioxide nanoparticles on human bone marrow stromal cells

Abstract

Titanium dioxide nanoparticles (TiO2 NPs) have attracted substantial attention in various applications, including environmental remediation and nanomedicine. A detailed understanding of the toxicity of TiO2 NPs and the underlying mechanisms is fundamental to further development of their environmental and biomedical applications. Herein, we determined the changes in the transcriptional profile of human bone marrow stromal cells (BMSCs) after a set of different sized TiO2 NPs exposure using single-cell RNA-seq (scRNA-seq). By taking advantage of sensitivity of scRNA-seq, we found that TiO2 NPs exposure led to profound changes in gene expression and DNA damage signaling played a pivotal role in cellular responses to TiO2 NPs exposure. Smaller TiO2 NPs (5, 14 nm) led to a response similar to antivirus defense, and bigger TiO2 NPs (54, 135, and 228 nm) induced proliferation and differentiation changes in transcriptional levels. Validation experiments on representative genes showed that some genes might be served as biomarkers of TiO2 NPs exposure. Furthermore, in vitro and in vivo analyses showed remarkable over-production of reactive oxygen species (ROS) but did not affect osteogenic differentiation potential in BMSCs. The results unveiled landscape changes in transcriptomes in BMSCs induced by TiO2 NPs, which provides new insights into toxicity assessments of nanomaterials.