{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:15:35Z","timestamp":1788308135347,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005155","name":"Azrieli Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2054\/22"],"award-info":[{"award-number":["2054\/22"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["3605\/21"],"award-info":[{"award-number":["3605\/21"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["UKRI1687"],"award-info":[{"award-number":["UKRI1687"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Polyploidy is normally found in numerous tissues and cell types in the generally diploid human body and is crucial for proper development. However, polyploidy, and especially triploidy, can also be found in malignant tumours and is often associated with chemoresistance, stemness and metastatic capabilities. Here, we utilise our isogenic haploid, diploid and triploid human embryonic stem cell (hESC) lines to study the effect of ploidy on the response to four different anticancer drugs. Surprisingly, we show that triploid cells are more sensitive to chemotherapy\u2010induced apoptosis and cell cycle arrest than diploid and haploid cells, correlated with higher levels of DNA damage. This phenotype is regulated by p53, as it was reversed in\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010KO cells, where triploid mutant cells display higher resistance to the chemotherapies we applied compared to mutant haploid and diploid cells. The reversal from sensitivity to resistance, driven by\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010KO of the triploid cells, was accompanied by a reversal in the enrichment of DNA repair, replication and cell division related genes, compared to their diploid counterparts. Conversely, triploidy triggered DNA damage\u2010induced differentiation in both WT and\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010KO treated cells, pointing to a ploidy\u2010dependent response not mediated by p53. In addition, we show that cancer cell lines also display similar ploidy\u2010dependent anticancer drug responses to our\n                    <jats:italic>TP53<\/jats:italic>\n                    \u2010KO hESCs. These findings uncover the interplay between ploidy and the p53 pathway in determining the outcome of anticancer therapeutics, and display the potential use of isogenic hESCs, differing only in their ploidy level, in studying the impact of ploidy on chemotherapy response.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70278","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:40:22Z","timestamp":1788306022000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ploidy\u2010Dependent Response to Anticancer Drugs of Human Embryonic Stem Cells"],"prefix":"10.1111","author":[{"given":"Guy","family":"Haim\u2010Abadi","sequence":"first","affiliation":[{"name":"The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences The Hebrew University  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8234-2685","authenticated-orcid":false,"given":"Nissim","family":"Benvenisty","sequence":"additional","affiliation":[{"name":"The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences The Hebrew University  Jerusalem 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