Single-cell RNA sequencing reveals placental response under environmental stress

• Published in: Nature communications Vol. 15; no. 1; pp. 6549 - 18
• Main Authors: Van Buren, Eric, Azzara, David, Rangel-Moreno, Javier, Garcia-Hernandez, Maria de la Luz, Murphy, Shawn P, Cohen, Ethan D, Lewis, Ethan, Lin, Xihong, Park, Hae-Ryung
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 02.08.2024; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Arsenic; Arsenic - toxicity; Cell cycle; Cell Cycle - drug effects; Cell Cycle - genetics; Cell death; Cell proliferation; Cell Proliferation - drug effects; Cytotoxicity; Environmental impact; Environmental stress; Female; Fetuses; Gene expression; Gene sequencing; Humans; Impact analysis; Mice; Mice, Inbred C57BL; Placenta; Placenta - drug effects; Placenta - metabolism; Pregnancy; Pregnancy complications; Proteins; Ribonucleic acid; RNA; Sequence Analysis, RNA; Single-Cell Analysis; Stress, Physiological - genetics; Therapeutic targets; Trophoblasts - cytology; Trophoblasts - drug effects; Trophoblasts - metabolism; Up-Regulation - drug effects
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-50914-9

The placenta is crucial for fetal development, yet the impact of environmental stressors such as arsenic exposure remains poorly understood. We apply single-cell RNA sequencing to analyze the response of the mouse placenta to arsenic, revealing cell-type-specific gene expression, function, and pathological changes. Notably, the Prap1 gene, which encodes proline-rich acidic protein 1 (PRAP1), is significantly upregulated in 26 placental cell types including various trophoblast cells. Our study shows a female-biased increase in PRAP1 in response to arsenic and localizes it in the placenta. In vitro and ex vivo experiments confirm PRAP1 upregulation following arsenic treatment and demonstrate that recombinant PRAP1 protein reduces arsenic-induced cytotoxicity and downregulates cell cycle pathways in human trophoblast cells. Moreover, PRAP1 knockdown differentially affects cell cycle processes, proliferation, and cell death depending on the presence of arsenic. Our findings provide insights into the placental response to environmental stress, offering potential preventative and therapeutic approaches for environment-related adverse outcomes in mothers and children.