EGAGenomicsWhole Genome Sequencinghttps://ega-archive.org/studies/EGAS00001001561EGAEGA study EGAS00001001561PSCP_mutation analysis in hESCsEGArestrictedRNF53, Mutations, BRCC1, determination, IRIS, PNCA4, BRCAI, chemical analysis., PSCP, assay, BROVCA1, PPP1R53, FANCSSafeties, MGC130048, Materials, PhrB photolyase activity, determination, postnatal development, Stem Cells, A4, growth and development, Progress Reports, SCP1, CG30327, Tumor, type I programmed cell death, pigmented epithelium, brl, Long Term, Productivity, Publication., Embryonal Carcinomas, dmTAF[[II]]230, CG11478, School-Age, Background, Readability, Extrinsic Pathway Apoptoses, Summary Report, Cultural, Mother Cells, 3, Whole Transcriptome, Transcriptome Sequencing, NUP96, PAST, iPS cell, Effect, epithelium, Summary Reports, imprinted and ancient gene protein, Cell Division Cycles, average, gamma sarcoglycan, DmelCG42257, ethnicity, DLK-1, grafting, Man (Taxonomy), TFIID TAF250, Progress Report, Genomes, cel, Moods, Complete Exome Sequencing, Whole Transcriptome Sequencing, Delta1, pigmented retina, hES cell line cell, high grade, DNA cyclobutane dipyrimidine photolyase activity, Epigenomic, SUPPRESSOR OF AUXIN RESISTANCE 3, genetic, Progress, Intrinsic Pathway Apoptosis, Field Reports, malignant neoplasm, Classic, Human Embryonic Stem, Cell Cycles, Classical Apoptosis, Medicine, gamma-sarcoglycan, HPAST1, Malignancies, Medicines, Long-Term Effects, infrequent, single-organism behavior, Tumors, PRE, dTAF[[II]]230, Caspase-Dependent Apoptosis, Modern, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, Exome, familial, SG-gamma, Longterm Effect, TAF200, pref-1, TAFII-250, TAF250/230, Division Cycles, Expanded, Cultural Background, TAFII250, signaling (initiator) caspase activity, Benign, Colony-Forming Unit, induction of apoptosis, Investigative Report, Stem Cell, Cultures, retinal pigment, Intrinsic Pathway, School Age, Extrinsic Pathway Apoptosis, 1270, CG6393, dipyrimidine photolyase 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Transcriptome Sequencings, Apoptoses, TAF230, AW742678, big, d230, human being, SGCG_HUMAN, H-PAST, Effects, embryonal carcinoma, Complete Exome, low frequency, Neoplasms, Colony-Forming Units, caspase-dependent programmed cell death, Progenitor Cell, Benign Neoplasm, Caspase Dependent Apoptosis, Gene, dTAFII250, photoreactivating enzyme activity, Transplantations, Ximpact, EfW1, Malignant, activation of apoptosis, TYPE, Human, Regenerative, DAGA4, large, DmelCG4114, Investigative, Homo sapiens, Publication, dmTAF1, Taf230, Cycle, 35DAG, Mood, stratum pigmentosa retinae, Type I, MAM, gamma-SG, pG2, SCG3, Progenitor, Man, Backgrounds, TAF250, Cycles, School-Age Populations, Taf200, WES, Complete, MOS3, dTAF[[II]]250, Exome Sequencings, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Genetic, Malignancy, PRECOCIOUS, Longterm, cell, Ly107, Cell Division Cycle, cell-division cycle, F23A5.3, Mother, Cultural Relativisms, Taf1p, Cell Division, Long-Term, Population, apoptosis activator activity, Sequencing, Neoplasias, dTAF250, Scp-1, Whole Exome, RANDOM, Classic Apoptosis, 65K, great, Whole, CG42257, Dmel_CG30327, Customs, Long-Term Effect, snp, culture, School Age Population, Investigative Reports, TAF, constitutitional genetic, F23A5_3, Apoptosis, Cancer, cg11478, Colony Forming Unit, TAF[[II]]250, Complete Exome Sequencings, Malignant Neoplasm, 35 kDa dystrophin-associated glycoprotein, Affects, Progenitor Cells, CG4114, l(3)84Ab, function, BG:DS00004.13, Cultural Backgrounds, Cistrons, Cell, impact-a, SGCG, LGMD2C, dTAF230, development, Peg9, Exome Sequencing, MODIFIER OF SNC1, iPSC, MT, p230, Embryonal Carcinoma, Programmed Cell Death, Research Reports, Long Term Effects, chemical analysis, deoxyribonucleic photolyase activity, Neoplasm, TAF[[II]]250/230, imprinted and ancient gene protein homolog, IMPACT, TFIID, ZOG, Zog, Human Embryonic, Random selection by shearing, apoptosis signaling, Taf[[II]]250, primary cancer, DlkI, RPE, TAF[[II]]230, Complete Transcriptome Sequencing, Cytogenetic, apoptosis, DMDA1, photolyase activity, primary extragonadal embryonal carcinoma, postnatal growth, stem cell, TAF[II]250, Cancers, Understanding, School Age Populations, malignant tumor, hESC, Longterm Effects, Pref-1, p. pigmentosa retinae, Classic Apoptoses, l(2)01270, hESC line cell, DmelCG17603, Reports, apoptotic program, Modern Man, SCARMD2, commitment to apoptosis, Relativisms, deoxyribonucleate pyrimidine dimer lyase (photosensitive), assay, Relativism, Summary, Cultural Relativism, hereditary, growth, RWDD5, hESCs, Neoplasia, Field Report, TAF1falsePSCP mutation analysis in hESCsMany studies over the past 10 years, culminating in the recent report of the International Stem Cell Initiative (ISCI, 2011) have shown that hPSC acquire genetic and epigenetic changes during their time in culture. Many of the genetic changes are non-random and recurrent, probably because they provide a selective growth advantage to the undifferentiated cells. Some are shared by embryonal carcinoma cells, the malignant counterparts of ES cells. The origins of these growth advantages are poorly understood, but may come from altered cell cycle dynamics, resistance to apoptosis or altered patterns of differentiation. Less is known about the nature and consequences of epigenetic changes, but it is likely that these similarly affect hPSC behaviour; e.g., enhanced expression of DLK1, an imprinted gene, is associated with altered hPSC growth (Enver et al 2005). Inevitably, these genetic and epigenetic changes will impact on our ability to use hPSC for regenerative medicine, either because malignant transformation of the undifferentiated cells or their differentiated derivatives to be used for transplantation compromises safety, or because they impede the function of those differentiated derivatives, or because they affect the efficiency with which the undifferentiated cells can be expanded and differentiated into desired cell types. Focusing initially upon the existing clinical grade hESC lines, later moving to iPSC, we will Consolidate and extend knowledge of the rate, type and functional impact of the genetic variations that occur during hPSC culture. We will use whole genome and exome sequencing as well as SNP arrays, together with clonal analysis and other cytogenetics techniques. Common changes will be compared with those found in the normal human population, at low frequency in the original cell population or observed during iPSC generation in the HIPSCI project currently based at the WTSI. These studies will provide a better understanding of the range of genetic changes that occur in hPSC beyond the CNVs already identified. In conjunction with cancer genome resources and expertise at WTSI, bioinformatic analyses of these hPSC data will allow us to assess potential impact on hPSC behaviour pertinent to applications in regenerative medicine, notably the likelihood that specific changes arising in undifferentiated PSC cultures may be associated with potential malignant transformation of differentiated progeny. This data is part of a pre-publication release. For information on the proper use of pre-publication data shred by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/2019-07-24 09:54:08EGAS000010015619606EGAD00001002231EGAC00001000205