TDCPP promotes apoptosis and inhibits the calcium signaling pathway in human neural stem cells

Area of Science:

• Neuroscience
• Toxicology
• Stem Cell Biology

Background:

• Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) is a widely used organophosphorus flame retardant (OFR).
• Previous research indicates TDCPP may cause neurotoxicity, but the underlying mechanisms remain unclear.
• Human induced pluripotent stem cells (hiPSCs)-derived neural stem cells (hNSCs) offer a valuable in vitro model for investigating pollutant neurotoxicity.

Purpose of the Study:

• To investigate the neurotoxic effects of TDCPP on hNSCs.
• To elucidate the molecular mechanisms underlying TDCPP-induced neurotoxicity.
• To examine the impact of TDCPP on the calcium signaling pathway in hNSCs.

Main Methods:

• Utilized hiPSCs-derived hNSCs as an in vitro model.
• Assessed cell viability, reactive oxygen species (ROS) generation, cell cycle progression, and apoptosis.
• Performed transcriptome sequencing and KEGG enrichment analysis.
• Investigated intracellular calcium homeostasis and key signaling pathway components.

Main Results:

• TDCPP significantly inhibited hNSC viability, increased ROS production, induced S-phase cell cycle arrest, and promoted apoptosis.
• Transcriptome analysis identified 387 differentially expressed genes, with the calcium signaling pathway being the most enriched.
• TDCPP disrupted intracellular calcium homeostasis and impaired the Ca²⁺/CALM/CaN/CAMK signaling pathway, reducing NFATC2 and GSK3β expression.

Conclusions:

• TDCPP exhibits significant toxicity towards the calcium signaling pathway in human neural stem cells.
• These disruptions in calcium signaling may adversely affect human nervous system development.
• TDCPP poses a potential risk to neural development through its impact on critical cellular pathways.