PFOS disrupts key developmental pathways during hiPSC-derived cardiomyocyte differentiation in vitro

ElsevierVolume 85, December 2022, 105475Toxicology in VitroHighlights•

PFOS disrupts cardiac differentiation in hiPSCs from two different donors.

Transcriptomes vary significantly between hiPSC lines from different donors.

Between the two cell lines 135 DEGs were shared in response to PFOS exposure.

PFOS disrupts WNT, TGF, HH, and EGF signaling pathways in cardiomyocyte assay.

Non-canonical Wntsingle bondCa2+ signaling pathway is disrupted by PFOS exposure.

Abstract

Exposure to perfluorooctanesulfonic acid (PFOS) has been associated with congenital heart disease (CHD) and decreased birth weight. PFOS exposure can disrupt signaling pathways relevant for cardiac development in stem cell-derived cardiomyocyte assays, such as the PluriBeat assay, where spheroids of human induced pluripotent stem cells (hiPSCs) differentiate into contracting cardiomyocytes. Notably, cell line origin can also affect how the assay responds to chemical exposure. Herein, we examined the effect of PFOS on cardiomyocyte differentiation by transcriptomics profiling of two different hiPSC lines to see if they exhibit a common pattern of disruption. Two stages of differentiation were investigated: the cardiac progenitor stage and the cardiomyocyte stage. Many differentially expressed genes (DEGs) were observed between cell lines independent of exposure. However, 135 DEGs were identified as common between the two cell lines. Of these, 10 DEGs were associated with GO-terms related to the heart. PFOS exposure disrupted multiple signaling pathways relevant to cardiac development, including WNT, TGF, HH, and EGF. Of these pathways, genes related to the non-canonical WNTsingle bondCa2+ signaling was particularly affected. PFOS thus has the capacity to disrupt pathways important for cardiac development and function.

Keywords

Perfluorooctanesulfonic acid

In vitro

Spheroids

Development

© 2022 The Authors. Published by Elsevier Ltd.

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