{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T02:23:18Z","timestamp":1763259798424,"version":"build-2065373602"},"reference-count":100,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["LISBOA-01-0145-FEDER-031502","101002391"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-031502","101002391"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programa Operacional Regional de Lisboa (Lisboa 2020)","award":["LISBOA-01-0145-FEDER-031502","101002391"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-031502","101002391"]}]},{"name":"European Research Council (ERC)","award":["LISBOA-01-0145-FEDER-031502","101002391"],"award-info":[{"award-number":["LISBOA-01-0145-FEDER-031502","101002391"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human pluripotent stem cells (PSCs), which include both embryonic and induced pluripotent stem cells, are widely used in fundamental and applied biomedical research. They have been instrumental for better understanding development and cell differentiation processes, disease origin and progression and can aid in the discovery of new drugs. PSCs also hold great potential in regenerative medicine to treat or diminish the effects of certain debilitating diseases, such as degenerative disorders. However, some concerns have recently been raised over their safety for use in regenerative medicine. One of the major concerns is the fact that PSCs are prone to errors in passing the correct number of chromosomes to daughter cells, resulting in aneuploid cells. Aneuploidy, characterised by an imbalance in chromosome number, elicits the upregulation of different stress pathways that are deleterious to cell homeostasis, impair proper embryo development and potentiate cancer development. In this review, we will summarize known molecular mechanisms recently revealed to impair mitotic fidelity in human PSCs and the consequences of the decreased mitotic fidelity of these cells. We will finish with speculative views on how the physiological characteristics of PSCs can affect the mitotic machinery and how their suboptimal mitotic fidelity may be circumvented.<\/jats:p>","DOI":"10.3390\/ijms241511933","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:45:02Z","timestamp":1690332302000},"page":"11933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Compromised Mitotic Fidelity in Human Pluripotent Stem Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"In\u00eas","family":"Milagre","sequence":"first","affiliation":[{"name":"Cat\u00f3lica Biomedical Research Centre, Cat\u00f3lica Medical School, Universidade Cat\u00f3lica Portuguesa, 1649-023 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0564-058X","authenticated-orcid":false,"given":"Carolina","family":"Pereira","sequence":"additional","affiliation":[{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8293-8603","authenticated-orcid":false,"given":"Raquel A.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Cat\u00f3lica Biomedical Research Centre, Cat\u00f3lica Medical School, Universidade Cat\u00f3lica Portuguesa, 1649-023 Lisbon, Portugal"},{"name":"Instituto Gulbenkian de Ci\u00eancia, 2780-156 Oeiras, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/nrm3448","article-title":"Induced Pluripotent Stem Cells: The New Patient?","volume":"13","author":"Bellin","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1126\/science.282.5391.1145","article-title":"Embryonic Stem Cell Lines Derived from Human Blastocysts","volume":"282","author":"Thomson","year":"1998","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nature05944","article-title":"In Vitro Reprogramming of Fibroblasts into a Pluripotent ES-Cell-like State","volume":"448","author":"Wernig","year":"2007","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.stem.2020.09.014","article-title":"Pluripotent Stem Cell-Based Cell Therapy\u2014Promise and Challenges","volume":"27","author":"Yamanaka","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_8","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":"ref_9","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrm4025","article-title":"Short- and Long-Term Effects of Chromosome Mis-Segregation and Aneuploidy","volume":"16","author":"Santaguida","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"The International Stem Cell Initiative (2011). Screening Ethnically Diverse Human Embryonic Stem Cells Identifies a Chromosome 20 Minimal Amplicon Conferring Growth Advantage. Nat. Biotechnol., 29, 1132\u20131144.","DOI":"10.1038\/nbt.2051"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nbt.1835","article-title":"Karyotypic Abnormalities in Human Induced Pluripotent Stem Cells and Embryonic Stem Cells","volume":"29","author":"Taapken","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.stem.2010.07.017","article-title":"Identification and Classification of Chromosomal Aberrations in Human Induced Pluripotent Stem Cells","volume":"7","author":"Mayshar","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nbt922","article-title":"Recurrent Gain of Chromosomes 17q and 12 in Cultured Human Embryonic Stem Cells","volume":"22","author":"Draper","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/nbt.1890","article-title":"Recurrent Copy Number Variations in Human Induced Pluripotent Stem Cells","volume":"29","author":"Nisler","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nbt1285","article-title":"Adaptation to Culture of Human Embryonic Stem Cells and Oncogenesis in Vivo","volume":"25","author":"Baker","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.stem.2010.12.003","article-title":"Dynamic Changes in the Copy Number of Pluripotency and Cell Proliferation Genes in Human ESCs and IPSCs during Reprogramming and Time in Culture","volume":"8","author":"Laurent","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1042\/BST20200043","article-title":"Aneuploidy in Human Eggs: Contributions of the Meiotic Spindle","volume":"49","author":"Thomas","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41556-018-0243-8","article-title":"The Diverse Consequences of Aneuploidy","volume":"21","author":"Chunduri","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.ceb.2006.10.002","article-title":"Does Aneuploidy Cause Cancer?","volume":"18","author":"Weaver","year":"2006","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ccr.2008.11.011","article-title":"The Aneuploidy Paradox in Cell Growth and Tumorigenesis","volume":"14","author":"Weaver","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/embor.2012.55","article-title":"Losing Balance: The Origin and Impact of Aneuploidy in Cancer: \u2018Exploring Aneuploidy: The Significance of Chromosomal Imbalance\u2019 Review Series","volume":"13","author":"Holland","year":"2012","journal-title":"EMBO Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.stemcr.2016.01.015","article-title":"Higher-Density Culture in Human Embryonic Stem Cells Results in DNA Damage and Genome Instability","volume":"6","author":"Jacobs","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nrg3123","article-title":"Causes and Consequences of Aneuploidy in Cancer","volume":"13","author":"Gordon","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ceb.2010.08.007","article-title":"Mechanisms of Aneuploidy","volume":"23","author":"Compton","year":"2011","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrm2163","article-title":"The Spindle-Assembly Checkpoint in Space and Time","volume":"8","author":"Musacchio","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/978-3-319-58592-5_20","article-title":"Centromeric Cohesin: Molecular Glue and Much More","volume":"56","author":"Mirkovic","year":"2017","journal-title":"Prog. Mol. Subcell. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Piskadlo, E., and Oliveira, R.A. (2017). A Topology-Centric View on Mitotic Chromosome Architecture. IJMS, 18.","DOI":"10.3390\/ijms18122751"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.tig.2019.01.003","article-title":"Consequences of Genomic Diversification Induced by Segregation Errors","volume":"35","author":"Soto","year":"2019","journal-title":"Trends Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/jcp.20776","article-title":"Self-Renewal of Human Embryonic Stem Cells Is Supported by a Shortened G1 Cell Cycle Phase","volume":"209","author":"Becker","year":"2006","journal-title":"J. Cell. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.trsl.2014.03.004","article-title":"Epigenetic Regulation of Open Chromatin in Pluripotent Stem Cells","volume":"165","author":"Kobayashi","year":"2015","journal-title":"Transl. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.stem.2015.11.003","article-title":"Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects","volume":"18","author":"Lamm","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.stemcr.2020.04.004","article-title":"Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells","volume":"14","author":"Halliwell","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13287-017-0522-5","article-title":"DNA Double-Strand Breaks in Human Induced Pluripotent Stem Cell Reprogramming and Long-Term in Vitro Culturing","volume":"8","author":"Simara","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1002\/stem.2861","article-title":"High Basal Levels of \u0393H2AX in Human Induced Pluripotent Stem Cells Are Linked to Replication-Associated DNA Damage and Repair","volume":"36","author":"Vallabhaneni","year":"2018","journal-title":"Stem Cells"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kislova, A.V., Zheglo, D., Pozhitnova, V.O., Sviridov, P.S., Gadzhieva, E.P., and Voronina, E.S. (2023). Replication Stress Causes Delayed Mitotic Entry and Chromosome 12 Fragility at the ANKS1B Large Neuronal Gene in Human Induced Pluripotent Stem Cells. preprint.","DOI":"10.21203\/rs.3.rs-2781849\/v1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1038\/emboj.2013.211","article-title":"How Unfinished Business from S-Phase Affects Mitosis and Beyond","volume":"32","author":"Mankouri","year":"2013","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8036","DOI":"10.1038\/ncomms9036","article-title":"Limiting Replication Stress during Somatic Cell Reprogramming Reduces Genomic Instability in Induced Pluripotent Stem Cells","volume":"6","author":"Ruiz","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1002\/stem.1117","article-title":"Human Embryonic Stem Cells Fail to Activate CHK1 and Commit to Apoptosis in Response to DNA Replication Stress","volume":"30","author":"Desmarais","year":"2012","journal-title":"Stem Cells"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e202011014","DOI":"10.1083\/jcb.202011014","article-title":"Telomere Erosion in Human Pluripotent Stem Cells Leads to ATR-Mediated Mitotic Catastrophe","volume":"220","author":"Vessoni","year":"2021","journal-title":"J. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/bfgp\/elq038","article-title":"Chromatin Structure of Pluripotent Stem Cells and Induced Pluripotent Stem Cells","volume":"10","year":"2011","journal-title":"Brief. Funct. Genom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e51644","DOI":"10.15252\/embr.202051644","article-title":"Chromatin Accessibility Dynamics during Cell Fate Reprogramming","volume":"22","author":"Li","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.1244508","article-title":"A Cascade of Histone Modifications Induces Chromatin Condensation in Mitosis","volume":"343","author":"Wilkins","year":"2014","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nature19333","article-title":"Insights from Biochemical Reconstitution into the Architecture of Human Kinetochores","volume":"537","author":"Weir","year":"2016","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1101\/sqb.2010.75.038","article-title":"Centromere Identity, Function, and Epigenetic Propagation across Cell Divisions","volume":"75","author":"Black","year":"2010","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"200227","DOI":"10.1098\/rsob.200227","article-title":"Reprogramming of Human Cells to Pluripotency Induces CENP-A Chromatin Depletion","volume":"10","author":"Milagre","year":"2020","journal-title":"Open Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1091\/mbc.e13-01-0034","article-title":"Assembly in G1 Phase and Long-Term Stability Are Unique Intrinsic Features of CENP-A Nucleosomes","volume":"24","author":"Bodor","year":"2013","journal-title":"MBoC"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1083\/jcb.200701066","article-title":"Propagation of Centromeric Chromatin Requires Exit from Mitosis","volume":"176","author":"Jansen","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.devcel.2015.03.020","article-title":"DNA Sequence-Specific Binding of CENP-B Enhances the Fidelity of Human Centromere Function","volume":"33","author":"Fachinetti","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.stemcr.2019.01.013","article-title":"Anti-Apoptotic Mutations Desensitize Human Pluripotent Stem Cells to Mitotic Stress and Enable Aneuploid Cell Survival","volume":"12","author":"Zhang","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.stemcr.2022.12.008","article-title":"A Pluripotent Developmental State Confers a Low Fidelity of Chromosome Segregation","volume":"18","author":"Deng","year":"2023","journal-title":"Stem Cell Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.tcb.2011.01.003","article-title":"Merotelic Kinetochore Attachment: Causes and Effects","volume":"21","author":"Gregan","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fcell.2015.00014","article-title":"The Chromosomal Passenger Complex (CPC) as a Key Orchestrator of Orderly Mitotic Exit and Cytokinesis","volume":"3","author":"Kitagawa","year":"2015","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Vuku\u0161i\u0107, K., and Toli\u0107, I.M. (2022). Polar Chromosomes\u2014Challenges of a Risky Path. Cells, 11.","DOI":"10.3390\/cells11091531"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00441-021-03544-2","article-title":"The Specialized Mitotic Behavior of Human Embryonic Stem Cells","volume":"387","author":"Lyu","year":"2022","journal-title":"Cell Tissue Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"111524","DOI":"10.1016\/j.celrep.2022.111524","article-title":"BCAT1 Redox Function Maintains Mitotic Fidelity","volume":"41","author":"Francois","year":"2022","journal-title":"Cell Rep."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dou, Z., Prifti, D., Gui, P., Liu, X., Elowe, S., and Yao, X. (2019). Recent Progress on the Localization of the Spindle Assembly Checkpoint Machinery to Kinetochores. Cells, 8.","DOI":"10.3390\/cells8030278"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4518","DOI":"10.1182\/blood-2006-10-054247","article-title":"Checkpoint-Apoptosis Uncoupling in Human and Mouse Embryonic Stem Cells: A Source of Karyotpic Instability","volume":"109","author":"Mantel","year":"2007","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1002\/1873-3468.13862","article-title":"From Clocks to Dominoes: Lessons on Cell Cycle Remodelling from Embryonic Stem Cells","volume":"594","author":"Padgett","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-1-4939-0888-2_2","article-title":"Cell Cycle Regulation by Checkpoints","volume":"Volume 1170","author":"Noguchi","year":"2014","journal-title":"Cell Cycle Control"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.ccr.2005.11.004","article-title":"Decatenation Checkpoint Deficiency in Stem and Progenitor Cells","volume":"8","author":"Damelin","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.devcel.2004.09.002","article-title":"Stuck in Division or Passing Through","volume":"7","author":"Rieder","year":"2004","journal-title":"Dev. Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/jcp.21925","article-title":"Human Embryonic Stem Cells Are Pre-Mitotically Committed to Self-Renewal and Acquire a Lengthened G1 Phase upon Lineage Programming","volume":"222","author":"Becker","year":"2010","journal-title":"J. Cell Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.scr.2007.09.002","article-title":"Differentiation Is Coupled to Changes in the Cell Cycle Regulatory Apparatus of Human Embryonic Stem Cells","volume":"1","author":"Filipczyk","year":"2007","journal-title":"Stem Cell Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cell.2013.08.031","article-title":"The Cell-Cycle State of Stem Cells Determines Cell Fate Propensity","volume":"155","author":"Pauklin","year":"2013","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.cell.2015.07.001","article-title":"Deterministic Restriction on Pluripotent State Dissolution by Cell-Cycle Pathways","volume":"162","author":"Gonzales","year":"2015","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1038\/ncb2129","article-title":"A Small GTPase Molecular Switch Regulates Epigenetic Centromere Maintenance by Stabilizing Newly Incorporated CENP-A","volume":"12","author":"Lagana","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.15252\/embj.201490649","article-title":"Reprogramming of Cell Fate: Epigenetic Memory and the Erasure of Memories Past","volume":"34","author":"Nashun","year":"2015","journal-title":"EMBO J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.celrep.2017.01.008","article-title":"Gender Differences in Global but Not Targeted Demethylation in IPSC Reprogramming","volume":"18","author":"Milagre","year":"2017","journal-title":"Cell Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5619","DOI":"10.1038\/ncomms6619","article-title":"An Epigenomic Roadmap to Induced Pluripotency Reveals DNA Methylation as a Reprogramming Modulator","volume":"5","author":"Lee","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.cell.2010.10.008","article-title":"Pluripotency and Cellular Reprogramming: Facts, Hypotheses, Unresolved Issues","volume":"143","author":"Hanna","year":"2010","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.cell.2015.06.016","article-title":"Integrative Analyses of Human Reprogramming Reveal Dynamic Nature of Induced Pluripotency","volume":"162","author":"Cacchiarelli","year":"2015","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.stem.2010.12.001","article-title":"Reprogramming Factor Expression Initiates Widespread Targeted Chromatin Remodeling","volume":"8","author":"Koche","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1074\/mcp.R115.054742","article-title":"Histone H4 Lysine 20 (H4K20) Methylation, Expanding the Signaling Potential of the Proteome One Methyl Moiety at a Time","volume":"15","author":"Gozani","year":"2016","journal-title":"Mol. Cell Proteom."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Andonegui-Elguera, M.A., C\u00e1ceres-Guti\u00e9rrez, R.E., L\u00f3pez-Saavedra, A., Cisneros-Soberanis, F., Justo-Garrido, M., D\u00edaz-Ch\u00e1vez, J., and Herrera, L.A. (2022). The Roles of Histone Post-Translational Modifications in the Formation and Function of a Mitotic Chromosome. IJMS, 23.","DOI":"10.3390\/ijms23158704"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/emboj.2010.329","article-title":"Epigenetic Engineering Shows H3K4me2 Is Required for HJURP Targeting and CENP-A Assembly on a Synthetic Human Kinetochore: H3K4me2 and Kinetochore Maintenance","volume":"30","author":"Bergmann","year":"2011","journal-title":"EMBO J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"13334","DOI":"10.1038\/ncomms13334","article-title":"Epigenetic Engineering Reveals a Balance between Histone Modifications and Transcription in Kinetochore Maintenance","volume":"7","author":"Molina","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/nature09272","article-title":"PHF8 Mediates Histone H4 Lysine 20 Demethylation Events Involved in Cell Cycle Progression","volume":"466","author":"Liu","year":"2010","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00412-016-0620-7","article-title":"Structure of Centromere Chromatin: From Nucleosome to Chromosomal Architecture","volume":"126","author":"Schalch","year":"2017","journal-title":"Chromosoma"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.devcel.2016.02.008","article-title":"HP1-Assisted Aurora B Kinase Activity Prevents Chromosome Segregation Errors","volume":"36","author":"Abe","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.tcb.2012.11.005","article-title":"Histone Modifications and Mitosis: Countermarks, Landmarks, and Bookmarks","volume":"23","author":"Wang","year":"2013","journal-title":"Trends Cell Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1242\/dev.142075","article-title":"Cycling through Developmental Decisions: How Cell Cycle Dynamics Control Pluripotency, Differentiation and Reprogramming","volume":"143","author":"Soufi","year":"2016","journal-title":"Development"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/nature09380","article-title":"Mediator and Cohesin Connect Gene Expression and Chromatin Architecture","volume":"467","author":"Kagey","year":"2010","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nbt.1527","article-title":"The Anti-Apoptotic Gene Survivin Contributes to Teratoma Formation by Human Embryonic Stem Cells","volume":"27","author":"Blum","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1146\/annurev.genet.42.110807.091711","article-title":"X Chromosome Dosage Compensation: How Mammals Keep the Balance","volume":"42","author":"Payer","year":"2008","journal-title":"Annu. Rev. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.devcel.2018.02.002","article-title":"Cellular Stress Associated with Aneuploidy","volume":"44","author":"Zhu","year":"2018","journal-title":"Dev. Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1101\/gr.276378.121","article-title":"Extensive Protein Dosage Compensation in Aneuploid Human Cancers","volume":"32","author":"Schukken","year":"2022","journal-title":"Genome Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e75526","DOI":"10.7554\/eLife.75526","article-title":"Regulation of Protein Complex Partners as a Compensatory Mechanism in Aneuploid Tumors","volume":"11","author":"Senger","year":"2022","journal-title":"eLife"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e75227","DOI":"10.7554\/eLife.75227","article-title":"Proteogenomic Analysis of Cancer Aneuploidy and Normal Tissues Reveals Divergent Modes of Gene Regulation across Cellular Pathways","volume":"11","author":"Cheng","year":"2022","journal-title":"eLife"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1126\/science.1160058","article-title":"Aneuploidy Affects Proliferation and Spontaneous Immortalization in Mammalian Cells","volume":"322","author":"Williams","year":"2008","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e05068","DOI":"10.7554\/eLife.05068","article-title":"Chromosome Mis-Segregation and Cytokinesis Failure in Trisomic Human Cells","volume":"4","author":"Nicholson","year":"2015","journal-title":"eLife"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1038\/s41467-020-17764-7","article-title":"Developmental Potential of Aneuploid Human Embryos Cultured beyond Implantation","volume":"11","author":"Shahbazi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/gcc.20574","article-title":"Tumor Progression of Culture-Adapted Human Embryonic Stem Cells during Long-Term Culture","volume":"47","author":"Yang","year":"2008","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_93","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":"Arad","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.15252\/embj.201593103","article-title":"Aneuploid Embryonic Stem Cells Exhibit Impaired Differentiation and Increased Neoplastic Potential","volume":"35","author":"Zhang","year":"2016","journal-title":"EMBO J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.stemcr.2023.04.001","article-title":"Generation, Genomic Characterization, and Differentiation of Triploid Human Embryonic Stem Cells","volume":"18","author":"Koren","year":"2023","journal-title":"Stem Cell Rep."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Mirkovic, M., Guilgur, L.G., Tavares, A., Passagem-Santos, D., and Oliveira, R.A. (2019). Induced Aneuploidy in Neural Stem Cells Triggers a Delayed Stress Response and Impairs Adult Life Span in Flies. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000016"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nature22312","article-title":"Human Pluripotent Stem Cells Recurrently Acquire and Expand Dominant Negative P53 Mutations","volume":"545","author":"Merkle","year":"2017","journal-title":"Nature"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41586-020-03114-6","article-title":"Aneuploidy Renders Cancer Cells Vulnerable to Mitotic Checkpoint Inhibition","volume":"590","author":"McFarland","year":"2021","journal-title":"Nature"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e49248","DOI":"10.15252\/embr.201949248","article-title":"Small-molecule Inhibition of Aging-associated Chromosomal Instability Delays Cellular Senescence","volume":"21","author":"Macedo","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.celrep.2016.10.030","article-title":"Adaptive Resistance to an Inhibitor of Chromosomal Instability in Human Cancer Cells","volume":"17","author":"Orr","year":"2016","journal-title":"Cell Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/11933\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:18:57Z","timestamp":1760127537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/15\/11933"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,25]]},"references-count":100,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijms241511933"],"URL":"https:\/\/doi.org\/10.3390\/ijms241511933","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,7,25]]}}}