Cadmium, a highly ubiquitous toxic heavy metal, has been widely recognized as an environmental and industrial pollutant, which confers serious threats to human health. The molecular mechanisms of the cadmium‐induced cardiotoxicity (CIC) have not been studied in human cardiomyocytes at the cellular level. Here we showed that human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) can recapitulate the CIC at the cellular level. The cadmium‐treated hPSC‐CMs exhibited cellular phenotype including reduced cell viability, increased apoptosis, cardiac sarcomeric disorganization, elevated reactive oxygen species, altered action potential profile and cardiac arrhythmias. RNA‐sequencing analysis revealed a differential transcriptome profile and activated MAPK signalling pathway in cadmium‐treated hPSC‐CMs, and suppression of P38 MAPK but not ERK MAPK or JNK MAPK rescued CIC phenotype. We further identified that suppression of PI3K/Akt signalling pathway is sufficient to reverse the CIC phenotype, which may play an important role in CIC. Taken together, our data indicate that hPSC‐CMs can serve as a suitable model for the exploration of molecular mechanisms underlying CIC and for the discovery of CIC cardioprotective drugs.

Although transgenic and knockout mice are widely used to study the specification and differentiation of oligodendrocyte precursor cells (OPCs), mouse primary OPCs are difficult to be purified and maintained, and many in vitro studies have to resort to rat OPCs as substitutes. In this study, we reported that mouse O4 negative early-stage OPCs can be obtained by culturing cortical tissue blocks, and the simultaneous treatment of OPCs with Platelet Derived Growth Factor-AA (PDGFaa), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) is the key for the propagation of mouse OPCs in culture. EGF was found to be a potent mitogen for OPCs and cooperate with PDGFaa to extend cell division and inhibit their differentiation. EGF also collaborates with PDGFaa and bFGF to convert bipolar or tripolar OPCs to more vital fibroblast-like OPCs without compromising their oligodendrocyte differentiation potential. In addition, EGF promoted the survival and proliferation of glial progenitor cells (GPCs) derived from primary OPC cultures, and a mixture of GPCs and OPCs can be obtained and propagated in the presence of EGF, bFGF, and PDGFaa. Once EGF is withdrawn, GPC population decreased sharply and fibroblast-like OPCs changed into typical OPCs morphology, then homogeneous OPCs were obtained subsequently.

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