F–53B and PFOS treatments skew human embryonic stem cell in vitro cardiac differentiation towards epicardial cells by partly disrupting the WNT signaling pathway. (June 2020)

• Record Type: Journal Article
• Authors: Yang, Renjun; Liu, Shuyu; Liang, Xiaoxing; Yin, Nuoya; Ruan, Ting; Jiang, Linshu; Faiola, Francesco
• Is Part Of: Environmental pollution. Volume 261(2020)
• Publication Date: 2020-06
• Subjects: F–53B -- PFOS -- Human embryonic stem cells -- Cardiac differentiation -- Epicardial; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2020.114153
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: F–53B and PFOS are two per- and polyfluoroalkyl substances (PFASs) widely utilized in the metal plating industry as mist suppressants. Recent epidemiological studies have linked PFASs to cardiovascular diseases and alterations in heart geometry. However, we still have limited understanding of the effects of F–53B and PFOS on the developing heart. In this study, we employed a human embryonic stem cell (hESC)-based cardiac differentiation system and whole transcriptomics analyses to evaluate the potential developmental cardiac toxicity of F–53B and PFOS. We utilized F–53B and PFOS concentrations of 0.1–60 μM, covering the levels detected in human blood samples. We demonstrated that both F–53B and PFOS inhibited cardiac differentiation and promoted epicardial specification via upregulation of the WNT signaling pathway. Most importantly, the effects of F–53B were more robust than those of PFOS. This was because F–53B treatment disrupted the expression of more genes and led to lower cardiac differentiation efficiency. These findings imply that F–53B may not be a safe replacement for PFOS. Graphical abstract: Image 1 Highlights: F–53B and PFOS inhibit cardiac differentiation and promote epicardiac specification. F–53B and PFOS affect cardiac differentiation by disrupting WNT, IGF, FGF and BMP signaling. F–53B may exert stronger developmental cardiac toxicity than PFOS. Abstract : F–53B and PFOS diminished cardiomyocyte specification efficiency while promoting hESC differentiation into epicardial cells, likely by activating the WNT signaling pathway.