Decoding Cellular Stress States for Toxicology Using Single-Cell Transcriptomics.

We applied the TempO-LINC platform to generate single-cell transcriptomic (SCTr) profiles of ~40,000 HepaRG cells exposed to etoposide, brefeldin A, cycloheximide, rotenone, tBHQ, troglitazone, and tunicamycin at three concentrations for 24 hours. SCTr enabled a detailed analysis of adaptive stress response pathways (SRPs), including the unfolded protein response (UPR), oxidative stress response (OSR), heat shock response (HSR), and DNA damage response (DDR). Troglitazone upregulated lipid metabolism genes (, ) along with HSR and UPR activation, with co-expression of , , and in subsets of cells.

TempO-seq and RNA-seq gene expression levels are highly correlated for most genes: A comparison using 39 human cell lines.

Recent advances in transcriptomics technologies allow for whole transcriptome gene expression profiling using targeted sequencing techniques, which is becoming increasingly popular due to logistical ease of data acquisition and analysis. As data from these targeted sequencing platforms accumulates, it is important to evaluate their similarity to traditional whole transcriptome RNA-seq. Thus, we evaluated the comparability of TempO-seq data from cell lysates to traditional RNA-Seq from purified RNA using baseline gene expression profiles.

High-Throughput Transcriptomics Screen of ToxCast Chemicals in U-2 OS Cells.

New approach methodologies (NAMs) aim to accelerate the pace of chemical risk assessment while simultaneously reducing cost and dependency on animal studies. High Throughput Transcriptomics (HTTr) is an emerging NAM in the field of chemical hazard evaluation for establishing in vitro points-of-departure and providing mechanistic insight. In the current study, 1201 test chemicals were screened for bioactivity at eight concentrations using a 24-h exposure duration in the human- derived U-2 OS osteosarcoma cell line with HTTr.

Searching for LINCS to Stress: Using Text Mining to Automate Reference Chemical Curation.

Adaptive stress response pathways (SRPs) restore cellular homeostasis following perturbation but may activate terminal outcomes like apoptosis, autophagy, or cellular senescence if disruption exceeds critical thresholds. Because SRPs hold the key to vital cellular tipping points, they are targeted for therapeutic interventions and assessed as biomarkers of toxicity. Hence, we are developing a public database of chemicals that perturb SRPs to enable new data-driven tools to improve public health.

Effects of chloride and ionic strength on physical morphology, dissolution, and bacterial toxicity of silver nanoparticles.

In this study, we comprehensively evaluate chloride- and ionic-strength-mediated changes in the physical morphology, dissolution, and bacterial toxicity of silver nanoparticles (AgNPs), which are one of the most-used nanomaterials. The findings isolate the impact of ionic strength from that of chloride concentration. As ionic strength increases, AgNP aggregation likewise increases (such that the hydrodynamic radius [HR] increases), fractal dimension (Df) strongly decreases (providing increased available surface relative to suspensions with higher Df), and the release of Ag(aq) increases.