Single-cell RNA sequencing reveals placental response under environmental stress

Eric Buren, David Azzara, Javier Rangel-Moreno, Maria de la Luz Garcia-Hernandez, Shawn P. Murphy, Ethan D. Cohen, Ethan Lewis, Xihong Lin and Hae-Ryung Park ()
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Eric Buren: Harvard T.H. Chan School of Public Health
David Azzara: University of Rochester
Javier Rangel-Moreno: University of Rochester
Maria de la Luz Garcia-Hernandez: University of Rochester
Shawn P. Murphy: University of Rochester
Ethan D. Cohen: University of Rochester
Ethan Lewis: University of Rochester
Xihong Lin: Harvard T.H. Chan School of Public Health
Hae-Ryung Park: University of Rochester

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-50914-9

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