Genomic stability in reprogramming.

The genetic stability of induced pluripotent stem (iPS) cells has a significant impact on their potential use in regenerative medicine and basic research. Analysis of the genomic integrity of iPS cells suggests a tendency to develop aberrations ranging from whole chromosome trisomies to single nucleotide mutations. Furthermore, fluctuations in telomere elongation and changes in mitochondrial DNA are also observed. Some mutations may already exist in the founder cells or result from prolonged culturing, however, many of the mutations occur during the reprogramming event. Thus, great care should be given to the initial characterization and subsequent culturing of new iPS cell lines in order to avoid the use of potentially aberrant cells.

[1]  Ira M. Hall,et al.  Genome sequencing of mouse induced pluripotent stem cells reveals retroelement stability and infrequent DNA rearrangement during reprogramming. , 2011, Cell stem cell.

[2]  Riitta Lahesmaa,et al.  Copy number variation and selection during reprogramming to pluripotency , 2011, Nature.

[3]  Mike J. Mason,et al.  Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. , 2009, Cell stem cell.

[4]  Michael J. Ziller,et al.  Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines , 2011, Cell.

[5]  J. Thomson,et al.  Embryonic stem cell lines derived from human blastocysts. , 1998, Science.

[6]  Yutao Du,et al.  Low incidence of DNA sequence variation in human induced pluripotent stem cells generated by nonintegrating plasmid expression. , 2012, Cell stem cell.

[7]  K. Kinzler,et al.  Detection and quantification of rare mutations with massively parallel sequencing , 2011, Proceedings of the National Academy of Sciences.

[8]  R. Stewart,et al.  Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells , 2011, Nature.

[9]  M. Kaufman,et al.  Establishment in culture of pluripotential cells from mouse embryos , 1981, Nature.

[10]  Christopher A. Miller,et al.  Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells. , 2012, Cell stem cell.

[11]  George M. Church,et al.  Elevated Coding Mutation Rate During the Reprogramming of Human Somatic Cells into Induced Pluripotent Stem Cells , 2012, Stem cells.

[12]  Hans Lehrach,et al.  Human Induced Pluripotent Stem Cells Harbor Homoplasmic and Heteroplasmic Mitochondrial DNA Mutations While Maintaining Human Embryonic Stem Cell–like Metabolic Reprogramming , 2011, Stem cells.

[13]  M. Blasco,et al.  Telomere rejuvenation during nuclear reprogramming. , 2010, Current opinion in genetics & development.

[14]  N. Benvenisty,et al.  The tumorigenicity of human embryonic and induced pluripotent stem cells , 2011, Nature Reviews Cancer.

[15]  M. Lynch.  Rate, molecular spectrum, and consequences of human mutation , 2010, Proceedings of the National Academy of Sciences.

[16]  M. Sadelain,et al.  Generation of transgene-free human induced pluripotent stem cells with an excisable single polycistronic vector , 2011, Nature Protocols.

[17]  G. Wang,et al.  Recurrent trisomy and Robertsonian translocation of chromosome 14 in murine iPS cell lines , 2011, Chromosome Research.

[18]  G. Daley,et al.  Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. , 2010, Cell stem cell.

[19]  Y. Segev,et al.  Reprogramming of telomeric regions during the generation of human induced pluripotent stem cells and subsequent differentiation into fibroblast-like derivatives , 2011, Epigenetics.

[20]  S. Suhr,et al.  Telomere Dynamics in Human Cells Reprogrammed to Pluripotency , 2009, PloS one.

[21]  G. Daley,et al.  The promise of induced pluripotent stem cells in research and therapy , 2012, Nature.

[22]  Richard A Young,et al.  Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. , 2010, Cell stem cell.

[23]  N. Benvenisty,et al.  The tumorigenicity of diploid and aneuploid human pluripotent stem cells , 2009, Cell cycle.

[24]  M. Blasco,et al.  Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. , 2009, Cell stem cell.

[25]  E. Snyder,et al.  Spontaneous reversal of the developmental aging of normal human cells following transcriptional reprogramming. , 2010, Regenerative medicine.

[26]  N. Benvenisty,et al.  High Prevalence of Evolutionarily Conserved and Species‐Specific Genomic Aberrations in Mouse Pluripotent Stem Cells , 2012, Stem cells.

[27]  T. Cech,et al.  Telomere shortening and loss of self-renewal in dyskeratosis congenita iPS cells , 2011, Nature.

[28]  N. Benvenisty,et al.  Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. , 2011, Cell stem cell.

[29]  G. Daley,et al.  Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients , 2009, Nature.

[30]  F. Alt,et al.  Excision of Reprogramming Transgenes Improves the Differentiation Potential of iPS Cells Generated with a Single Excisable Vector , 2009, Stem cells.

[31]  P G Pelicci,et al.  Genomic instability in induced stem cells , 2011, Cell Death and Differentiation.

[32]  K. Hochedlinger,et al.  Induced pluripotency: history, mechanisms, and applications. , 2010, Genes & development.

[33]  K. Hochedlinger,et al.  Epigenetic reprogramming and induced pluripotency , 2009, Development.

[34]  Yoav Mayshar,et al.  Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. , 2010, Cell stem cell.

[35]  A. Meissner.  Epigenetic modifications in pluripotent and differentiated cells , 2010, Nature Biotechnology.

[36]  Jun S. Song,et al.  Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells , 2011, Nature Cell Biology.

[37]  J. Thomson,et al.  Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells , 2004, Nature Biotechnology.

[38]  K. Vrana,et al.  Robust activation of the human but not mouse telomerase gene during the induction of pluripotency , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[39]  Brian E. McIntosh,et al.  Genetic correction and analysis of induced pluripotent stem cells from a patient with gyrate atrophy , 2011, Proceedings of the National Academy of Sciences.

[40]  Jennifer M. Bolin,et al.  Proteomic and phosphoproteomic comparison of human ES and iPS cells , 2011, Nature Methods.

[41]  M. Lalande,et al.  Recurrent copy number variations in human induced pluripotent stem cells , 2011, Nature Biotechnology.

[42]  E. Kirkness,et al.  Somatic coding mutations in human induced pluripotent stem cells , 2011, Nature.

[43]  F. Gourronc,et al.  Therapeutic opportunities: telomere maintenance in inducible pluripotent stem cells. , 2012, Mutation research.

[44]  G. Daley,et al.  Induced pluripotent stem cells for modelling human diseases , 2011, Philosophical Transactions of the Royal Society B: Biological Sciences.

[45]  Yoav Mayshar,et al.  Large-scale analysis reveals acquisition of lineage-specific chromosomal aberrations in human adult stem cells. , 2011, Cell stem cell.

[46]  Julie V. Harness,et al.  Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. , 2011, Cell stem cell.

[47]  J. C. Belmonte,et al.  Diseases in a dish: modeling human genetic disorders using induced pluripotent cells , 2011, Nature Medicine.

[48]  P. Andrews,et al.  Adaptation to culture of human embryonic stem cells and oncogenesis in vivo , 2007, Nature Biotechnology.

[49]  M. Newton,et al.  Karyotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells , 2011, Nature Biotechnology.

[50]  Lucio Luzzatto,et al.  A quantitative measurement of the human somatic mutation rate. , 2005, Cancer research.

[51]  Martin J. Aryee,et al.  Epigenetic memory in induced pluripotent stem cells , 2010, Nature.

[52]  Dong Ryul Lee,et al.  Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage , 2011, Nature Biotechnology.