2. Academic Validation
  3. F-53B and PFOS treatments skew human embryonic stem cell in vitro cardiac differentiation towards epicardial cells by partly disrupting the WNT signaling pathway

F-53B and PFOS treatments skew human embryonic stem cell in vitro cardiac differentiation towards epicardial cells by partly disrupting the WNT signaling pathway

  • Environ Pollut. 2020 Jun;261:114153. doi: 10.1016/j.envpol.2020.114153.
Renjun Yang 1,  Shuyu Liu 2,  Xiaoxing Liang 1,  Nuoya Yin 1,  Ting Ruan 1,  Linshu Jiang 3,  Francesco Faiola 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China; Wellcome Trust/CRUK Gurdon Institute, Department of Pathology, University of Cambridge, Cambridge, CB2 1QN, UK.
  • 3 Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, 102206, China.
  • 4 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: faiola@rcees.ac.cn.
PMID: 32088431 DOI: 10.1016/j.envpol.2020.114153
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.

Keywords

Cardiac differentiation; Epicardial; F–53B; Human embryonic stem cells; PFOS.

Figures
Products