{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Dr. Kevin Eggan"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000642"],"host":["EGA"],"description":["EGA DAC EGAC00001000642"],"repository":["EGA"],"email":["stemcellgenomes@fas.harvard.edu"],"pubmed_abstract":["Human pluripotent stem cells (hPS cells) can self-renew indefinitely, making them an attractive source for regenerative therapies. This expansion potential has been linked with the acquisition of large copy number variants that provide mutated cells with a growth advantage in culture. The nature, extent and functional effects of other acquired genome sequence mutations in cultured hPS cells are not known. Here we sequence the protein-coding genes (exomes) of 140 independent human embryonic stem cell (hES cell) lines, including 26 lines prepared for potential clinical use. We then apply computational strategies for identifying mutations present in a subset of cells in each hES cell line. Although such mosaic mutations were generally rare, we identified five unrelated hES cell lines that carried six mutations in the TP53 gene that encodes the tumour suppressor P53. The TP53 mutations we observed are dominant negative and are the mutations most commonly seen in human cancers. We found that the TP53 mutant allelic fraction increased with passage number under standard culture conditions, suggesting that the P53 mutations confer selective advantage. We then mined published RNA sequencing data from 117 hPS cell lines, and observed another nine TP53 mutations, all resulting in coding changes in the DNA-binding domain of P53. In three lines, the allelic fraction exceeded 50%, suggesting additional selective advantage resulting from the loss of heterozygosity at the TP53 locus. As the acquisition and expansion of cancer-associated mutations in hPS cells may go unnoticed during most applications, we suggest that careful genetic characterization of hPS cells and their differentiated derivatives be carried out before clinical use."],"pubmed_title":["Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations."],"pubmed_authors":["Merkle Florian T FT, Ghosh Sulagna S, Kamitaki Nolan N, Mitchell Jana J, Avior Yishai Y, Mello Curtis C, Kashin Seva S, Mekhoubad Shila S, Ilic Dusko D, Charlton Maura M, Saphier Genevieve G, Handsaker Robert E RE, Genovese Giulio G, Bar Shiran S, Benvenisty Nissim N, McCarroll Steven A SA, Eggan Kevin K"],"name_synonyms":["fbwd4, LYAM1, leukocyte-endothelial cell adhesion molecule 1, l(2)04454, DmelCG1772, dac, human being, Ly22, CIB1, axis, Modern, stalk, lymph node homing receptor, p21[dacapo], Scanning Transmission, dactylin, Human, E130112M23Rik, cdi4, Electron Microscopy, leukocyte adhesion molecule 1, Homo sapiens, ly-22, dactylyn, p21, LNHR, leukocyte surface antigen Leu-8., CG1772, FBWD4, Scanning Transmission Electron Microscopy, Cdi4, CDI4, p27, Decapo, primary stem, Man, CD62L, LECAM1, Man (Taxonomy), shsf3, LAM-1, shfm3, E(Sev-CycE)2B, TQ1, Fbw4, FBW4, human, culm, Dach, CDKN2B, lymphocyte antigen 22, SHFM3, CD62 antigen-like family member L, Dac, DAC, p27[Dap], primary axis, dacapo/cyclin-dependent kinase interactor 4, AI182278, Modern Man, STEM, lymphocyte surface MEL-14 antigen, Dap, CES5A1, SELL, P15, fbw4, gp90-MEL, SHSF3"],"pubmed_title_synonyms":["beta-Tub60D, beta[[3]]-Tub, CG10873, DmelCG17117, dp53, Dmbeta3, human being, Dm-HTH, p50, Modern, p53, BETA 60D, Stem Cells, prac, beta3t, beta3-Tub, 143391_i_at, beta3 TU, Pluripotent, LFS1, betaTub3, Tp53, l(3)05745, Xp53, Human, 3t, DMP53, Homo sapiens, Stem Cell, bbl, p53/tubulin, Pluripotent Stem Cell, Dmp53, bfy, Mutations., beta[[3]] tubulin, anon-EST:Liang-2.13, Man, Tub60D, HTH, Hth, CG33336, beta-tub, 1323/07, Man (Taxonomy), clone 2.13, BCC7, D.m.BETA-60D, beta-Tub6D, dmp53, DmelCG33336, D-p53, beta60C, CG3401, beta3Tub, beta3TUB, T, DmP53, Dm-P53, l(3)86Ca, 1422/04, beta3, human, dtl, Tub, DTB3, B3t, Meis1, DmelCG3401, hth1, Trp53, hth2, Dp53, betatub60D, Modern Man, P53, betaTub60C, p44, bhy, beta3-tubulin, beta[[3]]-tubulin, TRP53, CG17117, CG31325, betaTub, p50/tubulin"],"pubmed_abstract_synonyms":["extent, dp53, Materials, RNA Sequence Determination, acetylglucosaminyltransferase-like protein, Sequence Determination, postnatal development, RNA Sequence, Stem Cells, Mbp1, growth and development, l(3)96Fd, eosinophilia, Tumor, human embryonic stem cell, betaTub3, Tp53, Mutations, dmTAF[[II]]230, Background, DMP53, bbl, Cultural, Line, RRp, Dmp53, HLHm8, Analysis, myd, 1323/07, increased, ethnicity, thymus nucleic acid, Man (Taxonomy), like-acetylglucosaminyltransferase, TFIID TAF250, HPS, Genomes, BCC7, Analyses, cel, Determination, beta-Tub6D, dmp53, Mbp-1, CLAC, T, DmP53, 1422/04, Sequence Determinations, genetic, BNIP-H, B3t, DmelCG3401, Dp53, malignant neoplasm, Hermansky Pudlak syndrome, Human Embryonic Stem, Double-Stranded DNA, Malignancies, idiopathic, deoxyribonucleic acids, DNAn, associated, CG17117, protein-coding, p50/tubulin, Tumors, spnE, CG10873, dTAF[[II]]230, ES|130, gyltl1b-b, completeness, Modern, fs(1)hls, familial, TAF200, Double-Stranded, His-Purkinji network, TAFII-250, TAF250/230, not genetically inherited, Determinations, 3t, (Deoxyribonucleotide)n+m, Cultural Background, TAFII250, Benign, Stem Cell, Cultures, Su(H)[[m8]], MDDGA6, mKIAA0609, Genetic Materials, bfy, KIAA0609, desoxyribose nucleic acid, acetylglucosaminyltransferase-like 1A, Genetic Material, Tub60D, HTH, Hth, Lines, fg, beta-tub, Heterozygosity Loss, gyltl1b, Cultural Beliefs, growth pattern, non-developmental growth, 3322401A10Rik, mdc1d, DmelCG33336, Exomes, CG3401, beta3Tub, beta3TUB, Benign Neoplasms, hypereosinophilic syndrome, spn-E/hls, INSDC_feature:gene, whole genome, CG17603, LARGE_HUMAN, TAF[[II]], human, Malignant Neoplasms, DTB3, Hanta virus, MDC1D, hth1, E(spl)bHLH, hth2, enr, anon-EST:Liang-1.71, Human Embryonic Stem Cell, Taf250, Material, SR3-5, Cells, ds DNA, P53, p44, bhy, Cistron, inherited genetic, DNA, Hes, HES, other neoplasm, CG31325, TAF230, betaTub, accessory, beta[[3]]-Tub, DmelCG17117, d230, human being, DmelCG3158, DNS, CG8365, En(spl)-C, p50, (Deoxyribonucleotide)n, ES/130, Neoplasms, p53, number, Benign Neoplasm, ES130, Gene, dTAFII250, 143391_i_at, hes, hES, beta3 TU, EfW1, LFS1, Malignant, LARGE1, presence, supernumerary, froggy, l(3)05745, Deoxyribonucleic acids, Gyltl1a, spn E, Human, Homo sapiens, Deoxyribonucleic Acid, dmTAF1, Taf230, ADTB3A, Heterozygosity, Pluripotent Stem Cell, Cell., ADTB3, anon-EST:Liang-2.13, Man, Backgrounds, E(spl) m8, ji, TAF250, Taf200, VCS, dTAF[[II]]250, Genetic, clone 2.13, Malignancy, cell, MDDGB6, D.m.BETA-60D, ligand, Double Stranded, Cultural Relativisms, Taf1p, LARGE, Deoxyribonucleic acid, Sequencing, Neoplasias, BPFD#36, dTAF250, E(Spl), Trp53, HPS2, RNA Sequence Analyses, Espl, m8, betaTub60C, Customs, RNA Sequencing, beta3-tubulin, En(spl), E(spl), beta[[3]]-tubulin, (Deoxyribonucleotide)m, culture, TRP53, BB077577, Allelic Loss, TAF, constitutitional genetic, Sequence Analyses, Cancer, beta-Tub60D, RNA, TAF[[II]]250, Dmbeta3, Dm-HTH, Malignant Neoplasm, M8, RNA Sequence Determinations, DNAn+1, BETA 60D, E(spl)-C, prac, beta3t, beta3-Tub, clone 1.71, Cell Lines, l(3)84Ab, BG:DS00004.13, Loss of, Pluripotent, Cultural Backgrounds, DmelCG8365, Cistrons, Cell, Xp53, dTAF230, Allelic Losses, development, count in organism, MT, p230, p53/tubulin, CG3158, Neoplasm, sequence, TAF[[II]]250/230, TFIID, bHLHb36, rare (European definition), beta[[3]] tubulin, ds-DNA, Human Embryonic, SPN-E, Taf[[II]]250, CG33336, primary cancer, TAF[[II]]230, E(spl)m8, increased number, Spn-E, postnatal growth, D-p53, beta60C, Dm-P53, l(3)86Ca, TAF[II]250, beta3, Cancers, malignant tumor, primary structure of sequence macromolecule, hESC, dtl, Tub, spin-E, present in greater numbers in organism, Meis1, DmelCG17603, like-glycosyltransferase, homeless, ventricular conduction system, E(spl)-m8, E(spl)M8, betatub60D, Modern Man, RNA Sequence Analysis, cardinality, hls, Desoxyribonukleinsaeure, Relativisms, PE, fs(3)hls, Relativism, Cultural Relativism, growth, hereditary, hESCs, Neoplasia, glycosyltransferase-like protein LARGE1, e(spl), TAF1"],"additional_accession":[]},"is_claimable":false,"name":"DAC for Human Stem Sell Sequencing","description":"Data Access Committee EGAC00001000642","dates":{"output":"2025-1-9"},"accession":"EGAC00001000642","cross_references":{"TAXONOMY":["9606"],"pubmed":["28445466"],"EGA":["EGAS00001002400","EGAD00001003446"]}}