02391nas a2200193   4500008004100000022001400041245017300055210006900228260001600297300001100313520159800324100002301922700003501945700001701980700002101997700002002018700003002038856012902068       2023                        eng d  a1873-642400aPolystyrene nanoplastics affect transcriptomic and epigenomic signatures of human fibroblasts and derived induced pluripotent stem cells: Implications for human health.0 aPolystyrene nanoplastics affect transcriptomic and epigenomic si  c2022 Dec 09  a1208493 a<p>Plastic pollution is increasing at an alarming rate yet the impact of this pollution on human health is poorly understood. Because human induced pluripotent stem cells (hiPSC) are frequently derived from dermal fibroblasts, these cells offer a powerful platform for the identification of molecular biomarkers of environmental pollution in human cells. Here, we describe a novel proof-of-concept for deriving hiPSC from human dermal fibroblasts deliberately exposed to polystyrene (PS) nanoplastic particles; unexposed hiPSC served as controls. In parallel, unexposed hiPSC were exposed to low and high concentrations of PS nanoparticles. Transcriptomic and epigenomic signatures of all fibroblasts and hiPSCs were defined using RNA-seq and whole genome methyl-seq, respectively. Both PS-treated fibroblasts and derived hiPSC showed alterations in expression of ESRRB and HNF1A genes and circuits involved in the pluripotency of stem cells, as well as in pathways involved in cancer, inflammatory disorders, gluconeogenesis, carbohydrate metabolism, innate immunity, and dopaminergic synapse. Similarly, the expression levels of identified key transcriptional and DNA methylation changes (DNMT3A, ESSRB, FAM133CP, HNF1A, SEPTIN7P8, and TTC34) were significantly affected in both PS-exposed fibroblasts and hiPSC. This study illustrates the power of human cellular models of environmental pollution to narrow down and prioritize the list of candidate molecular biomarkers of environmental pollution. This knowledge will facilitate the deciphering of the origins of environmental diseases.</p>1 aStojkovic, Miodrag1 aGuzmán, Francisco, Manuel Ort1 aHan, Dongjun1 aStojkovic, Petra1 aDopazo, Joaquin1 aStankovic, Konstantina, M  uhttp://clinbioinfosspa.es/content/polystyrene-nanoplastics-affect-transcriptomic-and-epigenomic-signatures-human-fibroblasts