title: Induced pluripotent stem cell generation-associated point mutations arise during the initial stages of the conversion of these cells.
abstract: A large number of point mutations have been identified in induced pluripotent stem cell (iPSC) genomes to date. Whether these mutations are associated with iPSC generation is an important and controversial issue. In this study, we approached this critical issue in different ways, including an assessment of iPSCs versus embryonic stem cells (ESCs), and an investigation of variant allele frequencies and the heterogeneity of point mutations within a single iPSC clone. Through these analyses, we obtained strong evidence that iPSC-generation-associated point mutations occur frequently in a transversion-predominant manner just after the onset of cell lineage conversion. The heterogeneity of the point mutation profiles within an iPSC clone was also revealed and reflects the history of the emergence of each mutation. Further, our results suggest a possible approach for establishing iPSCs with fewer point mutations.
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors: Mayumi
authors: M
authors: Sugiura
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors: Yasuji
authors: Y
authors: Kasama
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors: Ryoko
authors: R
authors: Araki
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors: Yuko
authors: Y
authors: Hoki
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors: Misato
authors: M
authors: Sunayama
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors: Masahiro
authors: M
authors: Uda
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors: Miki
authors: M
authors: Nakamura
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors: Shunsuke
authors: S
authors: Ando
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba 263-8555, Japan.
authors: Masumi
authors: M
authors: Abe
mesh_terms: D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D016678:Genome; D059014:High-Throughput Nucleotide Sequencing; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017354:Point Mutation; D017422:Sequence Analysis, DNA