title: Methods of Reprogramming to Induced Pluripotent Stem Cell Associated with Chromosomal Integrity and Delineation of a Chromosome 5q Candidate Region for Growth Advantage.
abstract: Induced pluripotent stem cells (iPSCs) have brought great promises for disease modeling and cell-based therapies. One concern related to the use of reprogrammed somatic cells is the loss of genomic integrity and chromosome stability, a hallmark for cancer and many other human disorders. We investigated 16 human iPSC lines reprogrammed by nonintegrative Sendai virus (SeV) and another 16 iPSC lines generated by integrative lentivirus for genetic changes. At early passages we detected cytogenetic rearrangements in 44% (7/16) of iPSC lines generated by lentiviral integration whereas the corresponding figure was 6% (1/16) using SeV-based delivery. The rearrangements were numerical and/or structural with chromosomes 5 and 12 as the most frequently involved chromosomes. Three iPSC lines with chromosome 5 aberrations were derived from one and the same donor. We present in this study the aberrant karyotypes including a duplication of chromosome 5q13q33 that restricts a candidate region for growth advantage. Our results suggest that the use of integrative lentivirus confers a higher risk for cytogenetic abnormalities at early passages when compared to SeV-based reprogramming. In combination, our findings expand the knowledge on acquired cytogenetic aberrations in iPSC after reprogramming and during culture.
authors: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Biomedical Centre, Uppsala University , Uppsala, Sweden .
authors: Maria
authors: M
authors: Sobol
authors: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Biomedical Centre, Uppsala University , Uppsala, Sweden .
authors: Doroteya
authors: D
authors: Raykova
authors: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Biomedical Centre, Uppsala University , Uppsala, Sweden .
authors: Lucia
authors: L
authors: Cavelier
authors: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Biomedical Centre, Uppsala University , Uppsala, Sweden .
authors: Ayda
authors: A
authors: Khalfallah
authors: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Biomedical Centre, Uppsala University , Uppsala, Sweden .
authors: Jens
authors: J
authors: Schuster
authors: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Biomedical Centre, Uppsala University , Uppsala, Sweden .
authors: Niklas
authors: N
authors: Dahl
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D014161:Transduction, Genetic / Q000379:methods