박혜령 (University of Rochester)

한빛사논문

조회286

박혜령Hae-Ryung Park

University of Rochester

CV File 143 kb

Nat. Commun., Aug 02 2024, 15 (1) 6549 | https://doi.org/10.1038/s41467-024-50914-9 Single-cell RNA sequencing reveals placental response under environmental stress

Eric Van Buren¹, David Azzara², Javier Rangel-Moreno³, Maria de la Luz Garcia-Hernandez³, Shawn P. Murphy⁴, Ethan D. Cohen⁵, Ethan Lewis², Xihong Lin^1,6 & Hae-RyungPark²

¹Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

²Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.

³Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester, Rochester, NY, USA.

⁴Department of Obstetricsand Gynecology, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.

⁵Department of Pediatrics, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.

⁶Department of Statistics, Harvard University, Cambridge, MA, USA.

Corresponding author

Correspondence to Hae-Ryung Park.

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.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-05)
연구진국외 연구진
분야 생명과학 > 세포생물학

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