{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:20:58Z","timestamp":1791274858880,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In the field of disease modeling, induced pluripotent stem cells (iPSCs) have become an appealing choice, especially for diseases that do not have an animal model. They can be generated from patients with known clinical features and compared with cells from healthy controls to identify the biological bases of disease. This study was undertaken to determine the variability in iPSC lines derived from different individuals, with the aim of determining criteria for selecting iPSC lines for disease models. We generated and characterized 18 iPSC lines from eight donors and considered variability at three levels: (a) variability in the criteria that define iPSC lines as pluripotent cells, (b) variability in cell lines from different donors, and (c) variability in cell lines from the same donor. We found that variability in transgene expression and pluripotency marker levels did not prevent iPSCs from fulfilling all other criteria for pluripotency, including teratoma formation. We found low interindividual and interclonal variability in iPSCs that fulfilled the most stringent criteria for pluripotency, with very high correlation in their gene expression profiles. Interestingly, some cell lines exhibited reprogramming instability, spontaneously regressing from a fully to a partially reprogrammed state. This was associated with a low percentage of cells expressing the pluripotency marker stage-specific embryonic antigen-4. Our study shows that it is possible to define a similar \u201cground state\u201d for each cell line as the basis for making patient versus control comparisons, an essential step in order to identify disease-associated variability above individual and cell line variability.<\/jats:p>","DOI":"10.5966\/sctm.2012-0043","type":"journal-article","created":{"date-parts":[[2012,9,8]],"date-time":"2012-09-08T04:59:18Z","timestamp":1347080358000},"page":"641-650","source":"Crossref","is-referenced-by-count":76,"title":["Variability in the Generation of Induced Pluripotent Stem Cells: Importance for Disease Modeling"],"prefix":"10.1093","volume":"1","author":[{"given":"Alejandra M.","family":"Vitale","sequence":"first","affiliation":[{"name":"National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland, Australia"},{"name":"Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Matigian","sequence":"additional","affiliation":[{"name":"National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sugandha","family":"Ravishankar","sequence":"additional","affiliation":[{"name":"National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Bellette","sequence":"additional","affiliation":[{"name":"National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Wood","sequence":"additional","affiliation":[{"name":"National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst J.","family":"Wolvetang","sequence":"additional","affiliation":[{"name":"Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Mackay-Sim","sequence":"additional","affiliation":[{"name":"National Centre for Adult Stem Cell Research, Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,7]]},"reference":[{"key":"2021122705561750700_ref1","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.biocel.2011.03.013","article-title":"Induced pluripotent stem cells: A new technology to study human diseases","volume":"43","author":"Vitale","year":"2011","journal-title":"Int J Biochem Cell Biol"},{"key":"2021122705561750700_ref2","doi-asserted-by":"crossref","first-page":"e2412","DOI":"10.1371\/journal.pone.0002412","article-title":"Fibroblast and lymphoblast gene expression profiles in schizophrenia: Are non-neural cells informative?","volume":"3","author":"Matigian","year":"2008","journal-title":"PLoS One"},{"key":"2021122705561750700_ref3","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11626-010-9275-5","article-title":"Human embryonic stem cells carrying mutations for severe genetic disorders","volume":"46","author":"Frumkin","year":"2010","journal-title":"In Vitro Cell Dev Biol Anim"},{"key":"2021122705561750700_ref4","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/S1472-6483(10)61801-9","article-title":"Generation of a human embryonic stem cell line encoding the cystic fibrosis mutation deltaF508, using preimplantation genetic diagnosis","volume":"10","author":"Pickering","year":"2005","journal-title":"Reprod Biomed Online"},{"key":"2021122705561750700_ref5","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.cell.2008.07.041","article-title":"Disease-specific induced pluripotent stem cells","volume":"134","author":"Park","year":"2008","journal-title":"Cell"},{"key":"2021122705561750700_ref6","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1126\/science.1158799","article-title":"Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons","volume":"321","author":"Dimos","year":"2008","journal-title":"Science"},{"key":"2021122705561750700_ref7","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nature07677","article-title":"Induced pluripotent stem cells from a spinal muscular atrophy patient","volume":"457","author":"Ebert","year":"2009","journal-title":"Nature"},{"key":"2021122705561750700_ref8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09915","article-title":"Modeling schizophrenia using human induced pluripotent stem cells","volume":"473","author":"Brennand","year":"2011","journal-title":"Nature"},{"key":"2021122705561750700_ref9","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.cell.2009.02.013","article-title":"Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors","volume":"136","author":"Soldner","year":"2009","journal-title":"Cell"},{"key":"2021122705561750700_ref10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nbt.1783","article-title":"A functionally characterized test set of human induced pluripotent stem cells","volume":"29","author":"Boulting","year":"2011","journal-title":"Nat Biotechnol"},{"key":"2021122705561750700_ref11","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.stem.2009.11.009","article-title":"Technical challenges in using human induced pluripotent stem cells to model disease","volume":"5","author":"Saha","year":"2009","journal-title":"Cell Stem Cell"},{"key":"2021122705561750700_ref12","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1242\/dmm.005447","article-title":"Disease-specific, neurosphere-derived cells as models for brain disorders","volume":"3","author":"Matigian","year":"2010","journal-title":"Dis Model Mech"},{"key":"2021122705561750700_ref13","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.stem.2011.03.002","article-title":"A call for standardized naming and reporting of human ESC and iPSC lines","volume":"8","author":"Luong","year":"2011","journal-title":"Cell Stem Cell"},{"key":"2021122705561750700_ref14","doi-asserted-by":"crossref","first-page":"e21907","DOI":"10.1371\/journal.pone.0021907","article-title":"NRF2 activation restores disease related metabolic deficiencies in olfactory neurosphere-derived cells from patients with sporadic Parkinson's disease","volume":"6","author":"Cook","year":"2011","journal-title":"PLoS One"},{"key":"2021122705561750700_ref15","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/bioinformatics\/btn224","article-title":"Lumi: A pipeline for processing Illumina microarray","volume":"24","author":"Du","year":"2008","journal-title":"Bioinformatics"},{"key":"2021122705561750700_ref16","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.stem.2008.11.008","article-title":"Guidelines and techniques for the generation of induced pluripotent stem cells","volume":"3","author":"Maherali","year":"2008","journal-title":"Cell Stem Cell"},{"key":"2021122705561750700_ref17","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nmeth.1580","article-title":"A bioinformatic assay for pluripotency in human cells","volume":"8","author":"M\u00fcller","year":"2011","journal-title":"Nat Methods"},{"key":"2021122705561750700_ref18","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1002\/stem.762","article-title":"Concise review: The promise of human induced pluripotent stem cell-based studies of schizophrenia","volume":"29","author":"Brennand","year":"2011","journal-title":"Stem Cells"},{"key":"2021122705561750700_ref19","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/nbt.1580","article-title":"Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells","volume":"27","author":"Chan","year":"2009","journal-title":"Nat Biotechnol"},{"key":"2021122705561750700_ref20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nature08180","article-title":"Elite and stochastic models for induced pluripotent stem cell generation","volume":"460","author":"Yamanaka","year":"2009","journal-title":"Nature"},{"key":"2021122705561750700_ref21","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/nbt1109-997","article-title":"Watching reprogramming in real time","volume":"27","author":"Subramanyam","year":"2009","journal-title":"Nat Biotechnol"},{"key":"2021122705561750700_ref22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1242\/dev.020867","article-title":"Epigenetic reprogramming and induced pluripotency","volume":"136","author":"Hochedlinger","year":"2009","journal-title":"Development"},{"key":"2021122705561750700_ref23","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.cell.2005.08.020","article-title":"Core transcriptional regulatory circuitry in human embryonic stem cells","volume":"122","author":"Boyer","year":"2005","journal-title":"Cell"},{"key":"2021122705561750700_ref24","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.stem.2009.09.005","article-title":"Gold standards in the diamond age: The commodification of pluripotency","volume":"5","author":"Sipp","year":"2009","journal-title":"Cell Stem Cell"},{"key":"2021122705561750700_ref25","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.stem.2009.02.009","article-title":"Broader implications of defining standards for the pluripotency of iPSCs","volume":"4","author":"Daley","year":"2009","journal-title":"Cell Stem Cell"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2012-0043","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.5966%2Fsctm.2012-0043","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/1\/9\/641\/41883124\/stcltm_1_9_641.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/1\/9\/641\/41883124\/stcltm_1_9_641.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T02:46:44Z","timestamp":1642560404000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/1\/9\/641-650\/6385473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,1]]},"references-count":25,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2012,9,7]]},"published-print":{"date-parts":[[2012,9,1]]}},"URL":"https:\/\/doi.org\/10.5966\/sctm.2012-0043","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,9,1]]},"published":{"date-parts":[[2012,9,1]]}}}