EGAGenomicsMultiomicsIllumina HiSeq 2000;https://ega-archive.org/datasets/EGAD0000100038435EGA dataset EGAD00001000384EGAAssessment of genetic and epigenetic variation in human IPS cellsThe accuracy of replicating the genetic code is fundamental. DNA repair mechanisms protect the fidelity of the genome ensuring a low error rate between generations. This sustains the similarity of individuals whilst providing a repertoire of variants for evolution. The mutation rate in the human genome has recently been measured to be 50-70 de novo single nucleotide variants (SNVs) between generations. During development mutations accumulate in somatic cells so that an organism is a mosaic. However, variation within a tissue and between tissues has not been analysed. By reprogramming somatic cells into induced pluripotent stem cells (iPSCs), their genomes and the associated mutational history are captured. By sequencing the genomes of polyclonal and monoclonal somatic cells and derived iPSCs we have determined the mutation rates and show how the patterns change from a somatic lineage in vivo through to iPSCs. Somatic cells have a mutation rate of 14 SNVs per cell per generation while iPSCs exhibited a ten-fold lower rate. Analyses of mutational signatures suggested that deamination of methylated cytosine may be the major mutagenic source in vivo, whilst oxidative DNA damage becomes dominant in vitro. Our results provide insights for better understanding of mutational processes and lineage relationships between human somatic cells. Furthermore it provides a foundation for interpretation of elevated mutation rates and patterns in cancer.Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.Rouhani Foad J FJ, Nik-Zainal Serena S, Wuster Arthur A, Li Yilong Y, Conte Nathalie N, Koike-Yusa Hiroko H, Kumasaka Natsuhiko N, Vallier Ludovic L, Yusa Kosuke K, Bradley Allan AdTAF[[II]]230, TAF[[II]]250, d230, human being, Fibroblast-Derived IPS Cell, determination, Induced Pluripotent Stem Cell, IPS, familial, TAF200, Fibroblast Derived IPS Cells, l(3)84Ab, hiPSC, dTAFII250, BG:DS00004.13, Somatic Cells, TAFII-250, TAF250/230, EfW1, IPS Cells, Cell, dTAF230, Mutations, dmTAF[[II]]230, TAFII250, somatic cell, Fibroblast Derived Induced Pluripotent Stem Cells, dmTAF1, Taf230, p230, chemical analysis, TAF[[II]]250/230, TFIID, IPS Cell, TAF250, Taf[[II]]250, Fibroblast-Derived IPS Cells, Taf200, dTAF[[II]]250, TAF[[II]]230, TFIID TAF250, cel, cell, Fibroblast-Derived IPS, Taf1p, TAF[II]250, present in organism, Fibroblast-Derived, CG17603, Somatic Cell, man, TAF[[II]], human, Human Induced Pluripotent Stem Cells, genetic, dTAF250, DmelCG17603, TAF1., Taf250, SR3-5, Cells, Fibroblast-Derived Induced Pluripotent Stem Cells, inherited genetic, assay, TAF, Human Induced Pluripotent Stem Cell, constitutitional genetic, hereditary, TAF230, accumulated, TAF1Human Induced Pluripotent Stem Cells., Fibroblast-Derived IPS Cells, Fibroblast-Derived IPS Cell, Aspect, Induced Pluripotent Stem Cell, IPS, Fibroblast-Derived IPS, Lineages, Fibroblast Derived IPS Cells, hiPSC, Histories, Historical Aspects, Cell Lineages, historical aspects, Fibroblast-Derived, Historical Aspect, IPS Cells, Cell, Lineage, Fibroblast Derived Induced Pluripotent Stem Cells, historical notes, Cells, Fibroblast-Derived Induced Pluripotent Stem Cells, Aspects, Human Induced Pluripotent Stem Cell, IPS Cell, Historicalprojections, malignant Growth, d230, multi-cellular organism, human being, single-organism developmental process, Fibroblast-Derived IPS Cell, Induced Pluripotent Stem Cell, Aspect, Ass-1, lamellae, IPS, cell type cancer, Fibroblast Derived IPS Cells, hiPSC, dTAFII250, Foundation, EfW1, IPS Cells, process of organ, Mutation Frequency, Human, protrusion, Mutations, dmTAF[[II]]230, lamella, Readability, somatic cell, Rate, dmTAF1, Taf230, Code, AA408052, deamination, DNA Damage Response, fold, Mutation Frequencies, Low, animal, neoplasm, malignant tumour, TAF250, portion of tissue, Fibroblast-Derived IPS Cells, proportion, Taf200, me75, Injury, dTAF[[II]]250, Genetic, TFIID TAF250, Genomes, cel, cell, neoplasm (disease), Tissue, Taf1p, ridges, elevated, Histories, man, D17Mit170, T1, Human Induced Pluripotent Stem Cells, ASS, dTAF250, Human Genomes, malignant neoplasm, papilla, species, associated, Nucleotide, TAF, Frequency, laminae, high elevation, ratio, malignancy, dTAF[[II]]230, TAF[[II]]250, 4-amino-, anatomical protrusion, cou, body, malignant, anatomical process, lamina, CA., TAF200, flanges, l(3)84Ab, whole body, BG:DS00004.13, Somatic Cells, Historical Aspects, TAFII-250, Tl3, historical aspects, TAF250/230, Tl2, Historical Aspect, Cell, results, dTAF230, development, organism, TAFII250, Lr, MT, Human Genome, Fibroblast Derived Induced Pluripotent Stem Cells, Frequencies, p230, malignant neoplasm (disease), Mutation Rates, shelf, organ system cancer, tissue portion, TAF[[II]]250/230, TFIID, simple tissue, Mutation, IPS Cell, flange, organ process, Taf[[II]]250, DNA Injury, Rates, 2(1H)-Pyrimidinone, Genotoxic Stress, DNA Injuries, primary cancer, TAF[[II]]230, whole organism, Genetic Codes, shelves, Fibroblast-Derived IPS, proportionality, DNA Lesion, Deaminations, rate, TAF[II]250, Understanding, Somatic Cell, Fibroblast-Derived, CG17603, TAF[[II]], projection, ridge, malignant tumor, human, Codes, DNA Lesions, processes, process, DmelCG17603, Genotoxic, Taf250, spine, malignant neoplastic disease, SR3-5, historical notes, Koerper, Cells, Stress, Fibroblast-Derived Induced Pluripotent Stem Cells, Bra, quotient, processus, DNA, Aspects, Human Induced Pluripotent Stem Cell, cancer, TAF230, Historical, TAF10.00.00.00.00.0falseEGAS00001000492-sc-20130423 - samplesIn order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs but it is unlcear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.2017-07-26 15:39:24EGAD00001000384960627054363EGAC00001000205EGAS00001000492