{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:07:34Z","timestamp":1779311254523,"version":"3.51.4"},"reference-count":47,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000765","name":"University College London","doi-asserted-by":"publisher","award":["G1000730"],"award-info":[{"award-number":["G1000730"]}],"id":[{"id":"10.13039\/501100000765","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000765","name":"University College London","doi-asserted-by":"publisher","award":["P12761"],"award-info":[{"award-number":["P12761"]}],"id":[{"id":"10.13039\/501100000765","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000858","name":"University of Sheffield","doi-asserted-by":"publisher","award":["MR\/L012537\/1"],"award-info":[{"award-number":["MR\/L012537\/1"]}],"id":[{"id":"10.13039\/501100000858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000858","name":"University of Sheffield","doi-asserted-by":"publisher","award":["MR\/R015724\/1"],"award-info":[{"award-number":["MR\/R015724\/1"]}],"id":[{"id":"10.13039\/501100000858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019326","name":"UK Regenerative Medicine Platform","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019326","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007033","name":"Lincy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007557","name":"California Institute of Regenerative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007557","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007183","name":"University of California Santa Barbara","doi-asserted-by":"publisher","award":["LA1_C2-02086"],"award-info":[{"award-number":["LA1_C2-02086"]}],"id":[{"id":"10.13039\/100007183","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Stem Cell Reports"],"published-print":{"date-parts":[[2023,3]]},"DOI":"10.1016\/j.stemcr.2023.01.007","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T11:43:15Z","timestamp":1676547795000},"page":"782-797","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["The isochromosome 20q abnormality of pluripotent cells interrupts germ layer differentiation"],"prefix":"10.1016","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-1793","authenticated-orcid":false,"given":"Loriana","family":"Vitillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiha","family":"Anjum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoe","family":"Hewitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dylan","family":"Stavish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen","family":"Laing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Barbaric","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pete","family":"Coffey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.stemcr.2023.01.007_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.stemcr.2017.05.029","article-title":"Assessing the safety of human pluripotent stem cells and their derivatives for clinical applications","volume":"9","author":"Andrews","year":"2017","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.stemcr.2023.01.007_bib2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.stemcr.2013.10.005","article-title":"BCL-XL mediates the strong selective advantage of a 20q11.21 amplification commonly found in human embryonic stem cell cultures","volume":"1","author":"Avery","year":"2013","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.stemcr.2023.01.007_bib3","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.stemcr.2016.10.003","article-title":"Detecting genetic mosaicism in cultures of human pluripotent stem cells","volume":"7","author":"Baker","year":"2016","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.stemcr.2023.01.007_bib4","doi-asserted-by":"crossref","first-page":"4825","DOI":"10.1038\/ncomms5825","article-title":"Aneuploidy induces profound changes in gene expression, proliferation and tumorigenicity of human pluripotent stem cells","volume":"5","author":"Ben-David","year":"2014","journal-title":"Nat. Commun."},{"key":"10.1016\/j.stemcr.2023.01.007_bib5","doi-asserted-by":"crossref","first-page":"11165","DOI":"10.1038\/ncomms11165","article-title":"Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential","volume":"7","author":"Bolton","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.stemcr.2023.01.007_bib6","doi-asserted-by":"crossref","first-page":"33792","DOI":"10.1038\/srep33792","article-title":"Mislocalisation of BEST1 in iPSC-derived retinal pigment epithelial cells from a family with autosomal dominant vitreoretinochoroidopathy (ADVIRC)","volume":"6","author":"Carter","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.stemcr.2023.01.007_bib7","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/s41586-021-03345-1","article-title":"Inherent mosaicism and extensive mutation of human placentas","volume":"592","author":"Coorens","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.stemcr.2023.01.007_bib8","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nbt.4114","article-title":"Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration","volume":"36","author":"da Cruz","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib9","doi-asserted-by":"crossref","first-page":"e52504","DOI":"10.7554\/eLife.52504","article-title":"Derivation of trophoblast stem cells from naive human pluripotent stem cells","volume":"9","author":"Dong","year":"2020","journal-title":"Elife"},{"key":"10.1016\/j.stemcr.2023.01.007_bib10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1387\/ijdb.103177af","article-title":"Altered patterns of differentiation in karyotypically abnormal human embryonic stem cells","volume":"55","author":"Fazeli","year":"2011","journal-title":"Int. J. Dev. Biol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/humupd\/dmw026","article-title":"Stem cell insights into human trophoblast lineage differentiation","volume":"23","author":"Gamage","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"10.1016\/j.stemcr.2023.01.007_bib12","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/nbt0915-890","article-title":"RIKEN suspends first clinical trial involving induced pluripotent stem cells","volume":"33","author":"Garber","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib13","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.3390\/cells8121500","article-title":"TGFbeta family signaling pathways in pluripotent and teratocarcinoma stem cells' fate decisions: balancing between self-renewal, differentiation, and cancer","volume":"8","author":"Gordeeva","year":"2019","journal-title":"Cells"},{"key":"10.1016\/j.stemcr.2023.01.007_bib14","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.stem.2021.02.025","article-title":"Human naive epiblast cells possess unrestricted lineage potential","volume":"28","author":"Guo","year":"2021","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stemcr.2023.01.007_bib15","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41580-020-00292-z","article-title":"Acquired genetic changes in human pluripotent stem cells: origins and consequences","volume":"21","author":"Halliwell","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib16","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1038\/nbt.2051","article-title":"Screening ethnically diverse human embryonic stem cells identifies a chromosome 20\u00a0minimal amplicon conferring growth advantage","volume":"29","author":"Amps","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib17","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1093\/humupd\/dmx042","article-title":"Genetic and epigenetic factors which modulate differentiation propensity in human pluripotent stem cells","volume":"24","author":"Keller","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"10.1016\/j.stemcr.2023.01.007_bib18","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.stemcr.2020.06.014","article-title":"A manually curated database on clinical studies involving cell products derived from human pluripotent stem cells","volume":"15","author":"Kobold","year":"2020","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.stemcr.2023.01.007_bib19","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1158\/1535-7163.MCT-10-0609","article-title":"Nanaomycin A selectively inhibits DNMT3B and reactivates silenced tumor suppressor genes in human cancer cells","volume":"9","author":"Kuck","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.stemcr.2023.01.007_bib20","doi-asserted-by":"crossref","first-page":"e83","DOI":"10.1002\/cpsc.83","article-title":"Rapid PCR assay for detecting common genetic variants arising in human pluripotent stem cell cultures","volume":"49","author":"Laing","year":"2019","journal-title":"Curr. Protoc. Stem Cell Biol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib21","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1167\/iovs.14-15835","article-title":"Canonical\/beta-catenin Wnt pathway activation improves retinal pigmented epithelium derivation from human embryonic stem cells","volume":"56","author":"Leach","year":"2015","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.stemcr.2023.01.007_bib22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.stemcr.2016.01.006","article-title":"What is trophoblast? A combination of criteria define human first-trimester trophoblast","volume":"6","author":"Lee","year":"2016","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.stemcr.2023.01.007_bib23","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.celrep.2014.12.050","article-title":"Functional consequences of 17q21.31\/WNT3-WNT9B amplification in hPSCs with respect to neural differentiation","volume":"10","author":"Lee","year":"2015","journal-title":"Cell Rep."},{"key":"10.1016\/j.stemcr.2023.01.007_bib24","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nrg3271","article-title":"Genetic and epigenetic stability of human pluripotent stem cells","volume":"13","author":"Lund","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.stemcr.2023.01.007_bib25","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.3390\/jcm10081785","article-title":"Trends of stem cell therapies in age-related macular degeneration","volume":"10","author":"Maeda","year":"2021","journal-title":"J.\u00a0Clin. Med."},{"key":"10.1016\/j.stemcr.2023.01.007_bib26","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1056\/NEJMoa1608368","article-title":"Autologous induced stem-cell-derived retinal cells for macular degeneration","volume":"376","author":"Mandai","year":"2017","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.stemcr.2023.01.007_bib27","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.stemcr.2019.05.005","article-title":"Gain of 20q11.21 in human pluripotent stem cells impairs TGF-beta-dependent neuroectodermal commitment","volume":"13","author":"Markouli","year":"2019","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.stemcr.2023.01.007_bib28","doi-asserted-by":"crossref","first-page":"8242","DOI":"10.1038\/s41598-021-87547-7","article-title":"Sustained intrinsic WNT and BMP4 activation impairs hESC differentiation to definitive endoderm and drives the cells towards extra-embryonic mesoderm","volume":"11","author":"Markouli","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.stemcr.2023.01.007_bib29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.4161\/epi.7.1.18750","article-title":"Role of DNMT3B in the regulation of early neural and neural crest specifiers","volume":"7","author":"Martins-Taylor","year":"2012","journal-title":"Epigenetics"},{"key":"10.1016\/j.stemcr.2023.01.007_bib30","doi-asserted-by":"crossref","DOI":"10.1242\/dev.189746","article-title":"Retinal organoids: a window into human retinal development","volume":"147","author":"O'Hara-Wright","year":"2020","journal-title":"Development"},{"key":"10.1016\/j.stemcr.2023.01.007_bib31","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.scr.2009.09.001","article-title":"Modeling the evolution of culture-adapted human embryonic stem cells","volume":"4","author":"Olariu","year":"2010","journal-title":"Stem Cell Res."},{"key":"10.1016\/j.stemcr.2023.01.007_bib32","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1242\/dev.091769","article-title":"Activin\/Nodal signalling in stem cells","volume":"142","author":"Pauklin","year":"2015","journal-title":"Development"},{"key":"10.1016\/j.stemcr.2023.01.007_bib33","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/nature09228","article-title":"Extrinsic regulation of pluripotent stem cells","volume":"465","author":"Pera","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.stemcr.2023.01.007_bib34","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1016\/j.devcel.2021.07.019","article-title":"Genetically variant human pluripotent stem cells selectively eliminate wild-type counterparts through YAP-mediated cell competition","volume":"56","author":"Price","year":"2021","journal-title":"Dev. Cell"},{"key":"10.1016\/j.stemcr.2023.01.007_bib35","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13073-015-0183-x","article-title":"Restoration of mesenchymal retinal pigmented epithelial cells by TGFbeta pathway inhibitors: implications for age-related macular degeneration","volume":"7","author":"Radeke","year":"2015","journal-title":"Genome Med."},{"key":"10.1016\/j.stemcr.2023.01.007_bib36","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.tjog.2017.08.018","article-title":"Prenatal diagnosis of isochromosome 20q in a fetus with vertebral anomaly and rocker-bottom feet","volume":"56","author":"Receveur","year":"2017","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib37","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.jcyt.2019.10.001","article-title":"Tumorigenicity assessment of cell therapy products: the need for global consensus and points to consider","volume":"21","author":"Sato","year":"2019","journal-title":"Cytotherapy"},{"key":"10.1016\/j.stemcr.2023.01.007_bib38","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/nature10960","article-title":"A unique regulatory phase of DNA methylation in the early mammalian embryo","volume":"484","author":"Smith","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.stemcr.2023.01.007_bib39","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1242\/dev.096990","article-title":"RPE specification in the chick is mediated by surface ectoderm-derived BMP and Wnt signalling","volume":"140","author":"Steinfeld","year":"2013","journal-title":"Development"},{"key":"10.1016\/j.stemcr.2023.01.007_bib40","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nbt.1835","article-title":"Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells","volume":"29","author":"Taapken","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib41","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/s41467-020-15271-3","article-title":"Low rates of mutation in clinical grade human pluripotent stem cells under different culture conditions","volume":"11","author":"Thompson","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.stemcr.2023.01.007_bib42","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1080\/02713683.2019.1691237","article-title":"Treatment of age-related macular degeneration with pluripotent stem cell-derived retinal pigment epithelium","volume":"45","author":"Vitillo","year":"2020","journal-title":"Curr. Eye Res."},{"key":"10.1016\/j.stemcr.2023.01.007_bib43","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.expneurol.2008.09.007","article-title":"Elucidating the phenomenon of HESC-derived RPE: anatomy of cell genesis, expansion and retinal transplantation","volume":"214","author":"Vugler","year":"2008","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib44","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nbt.1516","article-title":"Characterization of human embryonic stem cells with features of neoplastic progression","volume":"27","author":"Werbowetski-Ogilvie","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib45","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1038\/bjc.2014.128","article-title":"Aza-deoxycytidine induces apoptosis or differentiation via DNMT3B and targets embryonal carcinoma cells but not their differentiated derivatives","volume":"110","author":"Wongtrakoongate","year":"2014","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.stemcr.2023.01.007_bib46","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/s41556-021-00660-7","article-title":"Depletion of aneuploid cells in human embryos and gastruloids","volume":"23","author":"Yang","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.stemcr.2023.01.007_bib47","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/s41586-021-03356-y","article-title":"Blastocyst-like structures generated from human pluripotent stem cells","volume":"591","author":"Yu","year":"2021","journal-title":"Nature"}],"container-title":["Stem Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213671123000103?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213671123000103?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:49:35Z","timestamp":1761990575000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213671123000103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["S2213671123000103"],"URL":"https:\/\/doi.org\/10.1016\/j.stemcr.2023.01.007","relation":{},"ISSN":["2213-6711"],"issn-type":[{"value":"2213-6711","type":"print"}],"subject":[],"published":{"date-parts":[[2023,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The isochromosome 20q abnormality of pluripotent cells interrupts germ layer differentiation","name":"articletitle","label":"Article Title"},{"value":"Stem Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.stemcr.2023.01.007","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors.","name":"copyright","label":"Copyright"}]}}