Dylan Stavish, Christopher J Price, Gabriele Gelezauskaite, Haneen Alsehli, Kimberly A Leonhard, Seth M Taapken, Erik M McIntire, Owen Laing, Bethany M James, Jack J Riley, Johanna Zerbib, Duncan Baker, Amy L Harding, Lydia H Jestice, Thomas F Eleveld, Ad J M Gillis, Sanne Hillenius, Leendert H J Looijenga, Paul J Gokhale, Uri Ben-David, Tenneille E Ludwig, Ivana Barbaric
{"title":"Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.","authors":"Dylan Stavish, Christopher J Price, Gabriele Gelezauskaite, Haneen Alsehli, Kimberly A Leonhard, Seth M Taapken, Erik M McIntire, Owen Laing, Bethany M James, Jack J Riley, Johanna Zerbib, Duncan Baker, Amy L Harding, Lydia H Jestice, Thomas F Eleveld, Ad J M Gillis, Sanne Hillenius, Leendert H J Looijenga, Paul J Gokhale, Uri Ben-David, Tenneille E Ludwig, Ivana Barbaric","doi":"10.1016/j.stemcr.2024.06.003","DOIUrl":null,"url":null,"abstract":"<p><p>Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"1217-1232"},"PeriodicalIF":5.9000,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368687/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cell Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stemcr.2024.06.003","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0
Abstract
Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection.
期刊介绍:
Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.