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The molecular mechanisms of the cadmium\u2010induced cardiotoxicity (<jats:styled-content style=\"fixed-case\">CIC<\/jats:styled-content>) have not been studied in human cardiomyocytes at the cellular level. Here we showed that human pluripotent stem cell\u2010derived cardiomyocytes (<jats:styled-content style=\"fixed-case\">hPSC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>s) can recapitulate the<jats:styled-content style=\"fixed-case\">CIC<\/jats:styled-content>at the cellular level. The cadmium\u2010treated<jats:styled-content style=\"fixed-case\">hPSC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>s exhibited cellular phenotype including reduced cell viability, increased apoptosis, cardiac sarcomeric disorganization, elevated reactive oxygen species, altered action potential profile and cardiac arrhythmias.<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010sequencing analysis revealed a differential transcriptome profile and activated<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>signalling pathway in cadmium\u2010treated<jats:styled-content style=\"fixed-case\">hPSC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>s, and suppression of P38<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>but not<jats:styled-content style=\"fixed-case\">ERK MAPK<\/jats:styled-content>or<jats:styled-content style=\"fixed-case\">JNK MAPK<\/jats:styled-content>rescued<jats:styled-content style=\"fixed-case\">CIC<\/jats:styled-content>phenotype. We further identified that suppression of<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt signalling pathway is sufficient to reverse the<jats:styled-content style=\"fixed-case\">CIC<\/jats:styled-content>phenotype, which may play an important role in<jats:styled-content style=\"fixed-case\">CIC<\/jats:styled-content>. Taken together, our data indicate that<jats:styled-content style=\"fixed-case\">hPSC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CM<\/jats:styled-content>s can serve as a suitable model for the exploration of molecular mechanisms underlying<jats:styled-content style=\"fixed-case\">CIC<\/jats:styled-content>and for the discovery of<jats:styled-content style=\"fixed-case\">CIC<\/jats:styled-content>cardioprotective drugs.<\/jats:p>","DOI":"10.1111\/jcmm.13702","type":"journal-article","created":{"date-parts":[[2018,7,11]],"date-time":"2018-07-11T11:22:04Z","timestamp":1531308124000},"page":"4221-4235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Modelling cadmium\u2010induced cardiotoxicity using human pluripotent stem cell\u2010derived cardiomyocytes"],"prefix":"10.1111","volume":"22","author":[{"given":"Jiaxi","family":"Shen","sequence":"first","affiliation":[{"name":"Key Laboratory of 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