title: An atypical human induced pluripotent stem cell line with a complex, stable, and balanced genomic rearrangement including a large de novo 1q uniparental disomy.
abstract: Human induced pluripotent stem cells (hiPSCs) hold great promise for cell therapy through their use as vital tools for regenerative and personalized medicine. However, the genomic integrity of hiPSCs still raises some concern and is one of the barriers limiting their use in clinical applications. Numerous articles have reported the occurrence of aneuploidies, copy number variations, or single point mutations in hiPSCs, and nonintegrative reprogramming strategies have been developed to minimize the impact of the reprogramming process on the hiPSC genome. Here, we report the characterization of an hiPSC line generated by daily transfections of modified messenger RNAs, displaying several genomic abnormalities. Karyotype analysis showed a complex genomic rearrangement, which remained stable during long-term culture. Fluorescent in situ hybridization analyses were performed on the hiPSC line showing that this karyotype is balanced. Interestingly, single-nucleotide polymorphism analysis revealed the presence of a large 1q region of uniparental disomy (UPD), demonstrating for the first time that UPD can occur in a noncompensatory context during nonintegrative reprogramming of normal fibroblasts.
authors: INSERM U972 and Unité Mixte de Recherche (UMR) S972, Université Paris-Sud, Paul Brousse Hospital, Villejuif, France; Département Hospitalo-universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France;
authors: Clara
authors: C
authors: Steichen
authors: INSERM UMR S986, Institut Fédératif de Recherche 93, Bicêtre Hospital, Kremlin-Bicêtre, France;
authors: Jérôme
authors: J
authors: Maluenda
authors: Department of Cytogenetics, Béclère Hospital, Clamart, France.
authors: Lucie
authors: L
authors: Tosca
authors: INSERM U972 and Unité Mixte de Recherche (UMR) S972, Université Paris-Sud, Paul Brousse Hospital, Villejuif, France; Département Hospitalo-universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France;
authors: Eléanor
authors: E
authors: Luce
authors: Department of Cytogenetics, Béclère Hospital, Clamart, France.
authors: Dominique
authors: D
authors: Pineau
authors: INSERM U972 and Unité Mixte de Recherche (UMR) S972, Université Paris-Sud, Paul Brousse Hospital, Villejuif, France; Département Hospitalo-universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France;
authors: Noushin
authors: N
authors: Dianat
authors: INSERM U972 and Unité Mixte de Recherche (UMR) S972, Université Paris-Sud, Paul Brousse Hospital, Villejuif, France; Département Hospitalo-universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France;
authors: Zara
authors: Z
authors: Hannoun
authors: Department of Cytogenetics, Béclère Hospital, Clamart, France.
authors: Gérard
authors: G
authors: Tachdjian
authors: INSERM UMR S986, Institut Fédératif de Recherche 93, Bicêtre Hospital, Kremlin-Bicêtre, France;
authors: Judith
authors: J
authors: Melki
authors: INSERM U972 and Unité Mixte de Recherche (UMR) S972, Université Paris-Sud, Paul Brousse Hospital, Villejuif, France; Département Hospitalo-universitaire Hepatinov, Paul Brousse Hospital, Villejuif, France; anne.dubart@inserm.fr.
authors: Anne
authors: A
authors: Dubart-Kupperschmitt
mesh_terms: D000782:Aneuploidy; D002460:Cell Line; D065150:Cellular Reprogramming; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005347:Fibroblasts / Q000473:pathology*; D015894:Genome, Human; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology*; D024182:Uniparental Disomy / Q000235:genetics* / Q000473:pathology
keywords: Abnormal karyotype; Directed differentiation; Genomic integrity; Induced pluripotent stem cells; Teratoma formation; Uniparental disomy
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