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

[Display omitted] • The genotoxicity of TiO 2 NPs was confirmed at the single-cell level. • CINP, RPA3, and PRKACA served as biomarkers of TiO2 NPs exposure. • 5 nm and 14 nm TiO 2 NPs caused a response similar to antivirus defense. • Unique gene expression patterns were found within the same exposure of TiO2 NPs. Titanium dioxide nanoparticles (TiO 2 NPs) have attracted substantial attention in various applications, including environmental remediation and nanomedicine. A detailed understanding of the toxicity of TiO 2 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 TiO 2 NPs exposure using single-cell RNA-seq (scRNA-seq). By taking advantage of sensitivity of scRNA-seq, we found that TiO 2 NPs exposure led to profound changes in gene expression and DNA damage signaling played a pivotal role in cellular responses to TiO 2 NPs exposure. Smaller TiO 2 NPs (5, 14 nm) led to a response similar to antivirus defense, and bigger TiO 2 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 TiO 2 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 TiO 2 NPs, which provides new insights into toxicity assessments of nanomaterials. [ABSTRACT FROM AUTHOR]