{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:40:36Z","timestamp":1792100436102,"version":"4.4.0"},"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T00:00:00Z","timestamp":1462233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research (BMBF)","award":["01GN0807"],"award-info":[{"award-number":["01GN0807"]}]},{"name":"German Federal Ministry of Education and Research (BMBF)","award":["01GN0807"],"award-info":[{"award-number":["01GN0807"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0154770","type":"journal-article","created":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T17:59:09Z","timestamp":1462298349000},"page":"e0154770","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":82,"title":["PI3K\/AKT Signaling Pathway Is Essential for Survival of Induced Pluripotent Stem Cells"],"prefix":"10.1371","volume":"11","author":[{"given":"Amir M.","family":"Hossini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika S.","family":"Quast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pl\u00f6tz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Grauel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarik","family":"Exner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"K\u00fcchler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Stachelscheid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Eberle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Rabien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia","family":"Makrantonaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos C.","family":"Zouboulis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,5,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"K Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/nprot.2008.92","article-title":"Generation of human-induced pluripotent stem cells","volume":"3","author":"IH Park","year":"2008","journal-title":"Nat Protoc"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"4530","DOI":"10.1093\/hmg\/ddr394","article-title":"Modeling familial Alzheimer's disease with induced pluripotent stem cells","volume":"20","author":"T Yagi","year":"2011","journal-title":"Hum Mol Genet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature10821","article-title":"Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells","volume":"482","author":"MA Israel","year":"2012","journal-title":"Nature"},{"issue":"1","key":"ref5","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s12864-015-1262-5","article-title":"Induced pluripotent stem cell-derived neuronal cells from a sporadic Alzheimer\u2019s disease donor as a model for investigating AD-associated gene regulatory network","volume":"16","author":"AM Hossini","year":"2015","journal-title":"BMC genomics"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13045-014-0050-z","article-title":"Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells","volume":"7","author":"J Li","year":"2014","journal-title":"J Hematol Oncol"},{"key":"ref7","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":"F Soldner","year":"2009","journal-title":"Cell"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nature10761","article-title":"The promise of induced pluripotent stem cells in research and therapy","volume":"481","author":"DA Robinton","year":"2012","journal-title":"Nature"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.molmed.2008.12.003","article-title":"Induced pluripotent stem cells: current progress and potential for regenerative medicine","volume":"15","author":"G Amabile","year":"2009","journal-title":"Trends Mol Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1007\/s12015-010-9148-z","article-title":"Selective removal of undifferentiated embryonic stem cells from differentiation cultures through HSV1 thymidine kinase and ganciclovir treatment","volume":"6","author":"O Naujok","year":"2010","journal-title":"Stem Cell"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/gcc.20574","article-title":"Tumor progression of culture-adapted human embryonic stem cells during long-term culture","volume":"47","author":"S Yang","year":"2008","journal-title":"Genes Chromosomes Cancer"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3822","DOI":"10.4161\/cc.8.23.10067","article-title":"The tumorigenicity of diploid and aneuploid human pluripotent stem cells","volume":"8","author":"B Blum","year":"2009","journal-title":"Cell cycle"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/carcin\/bgh283","article-title":"Apoptosis in the development and treatment of cancer","volume":"26","author":"R Gerl","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.drup.2007.09.001","article-title":"Overcoming apoptosis deficiency of melanoma-hope for new therapeutic approaches","volume":"10","author":"J Eberle","year":"2007","journal-title":"Drug Resist Updat"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.bcp.2008.08.013","article-title":"Apoptosis induction by Bcl-2 proteins independent of the BH3 domain","volume":"76","author":"AM Hossini","year":"2008","journal-title":"Biochem Pharmacol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/sj.cr.7310028","article-title":"How the Bcl-2 family of proteins interact to regulate apoptosis","volume":"16","author":"MF van Delft","year":"2006","journal-title":"Cell Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1046\/j.0022-202x.2001.01409.x","article-title":"The Bax\/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95\/Fas-mediated apoptosis","volume":"117","author":"M Raisova","year":"2001","journal-title":"J Invest Dermatol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S1471-4906(00)01814-7","article-title":"Caspases: more than just killers?","volume":"22","author":"M Los","year":"2001","journal-title":"Trends Immunol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.stem.2010.09.003","article-title":"Apoptotic caspases regulate induction of iPSCs from human fibroblasts","volume":"7","author":"F Li","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1089\/ten.teb.2012.0672","article-title":"The key regulatory roles of the PI3K\/Akt signaling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration","volume":"19","author":"J Chen","year":"2013","journal-title":"Tissue Eng Part B Rev"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1042\/BST0331522","article-title":"Role of the phosphoinositide 3-kinase pathway in mouse embryonic stem (ES) cells","volume":"33","author":"K Takahashi","year":"2005","journal-title":"Biochem Soc Trans"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1126\/science.278.5338.687","article-title":"Herrera R, Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt","volume":"278","author":"PL del","year":"1997","journal-title":"Science"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0092-8674(00)80405-5","article-title":"Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery","volume":"91","author":"SR Datta","journal-title":"Cell"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S1535-6108(04)00081-9","article-title":"Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt\/PKB pathway","volume":"5","author":"S Bao","year":"2004","journal-title":"Cancer Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nature02369","article-title":"Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy","volume":"428","author":"HG Wendel","year":"2004","journal-title":"Nature"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"e839","DOI":"10.1038\/cddis.2013.344","article-title":"ROS-dependent phosphorylation of Bax by wortmannin sensitizes melanoma cells for TRAIL-induced apoptosis","volume":"4","author":"SA Quast","journal-title":"Cell Death Dis. 2013"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/cr.2011.177","article-title":"The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming","volume":"22","author":"AD Panopoulos","year":"2012","journal-title":"Cell Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.scr.2014.03.002","article-title":"Mechanistic elements and critical factors of cellular reprogramming revealed by stepwise global gene expression analyses","volume":"12","author":"SJ Park","year":"2014","journal-title":"Stem Cell Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"5514","DOI":"10.1016\/j.biomaterials.2012.04.001","article-title":"Promotion of the induction of cell pluripotency through metabolic remodeling by thyroid hormone triiodothyronine-activated PI3K\/AKT signal pathway","volume":"33","author":"M Chen","year":"2012","journal-title":"Biomaterials"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.stem.2010.11.015","article-title":"Reprogramming of human primary somatic cells by OCT4 and chemical compounds","volume":"7","author":"S Zhu","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1111\/j.1474-9726.2011.00722.x","article-title":"Rapamycin and other longevity-promoting compounds enhance the generation of mouse induced pluripotent stem cells","volume":"10","author":"T Chen","year":"2011","journal-title":"Aging Cell"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/jid.2013.347","article-title":"RAF inhibition overcomes resistance to TRAIL-induced apoptosis in melanoma cells","volume":"134","author":"A Berger","year":"2014","journal-title":"J Invest Dermatol"},{"key":"ref33","first-page":"1377","article-title":"Aurora kinase A inhibitors: promising agents in antitumoral therapy","volume":"18","author":"M Malumbres","year":"2014","journal-title":"Expert Opin Ther Targets"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nrc821","article-title":"Targeting death and decoy receptors of the tumour-necrosis factor superfamily","volume":"2","author":"A Ashkenazi","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ijsu.2005.05.002","article-title":"An introduction to death receptors in apoptosis","volume":"3","author":"R Kumar","year":"2005","journal-title":"Int J Surg"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1038\/sj.onc.1210134","article-title":"Resistance of melanoma cells to TRAIL does not result from upregulation of antiapoptotic proteins by NF-kappaB but is related to downregulation of initiator caspases and DR4","volume":"26","author":"BM Kurbanov","year":"2007","journal-title":"Oncogene"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s10495-015-1114-4","article-title":"A novel dithiocarbamate derivative induces cell apoptosis through p53-dependent intrinsic pathway and suppresses the expression","volume":"20","author":"Y Li","year":"2015","journal-title":"Apoptosis"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.stem.2010.01.003","article-title":"Conserved and divergent roles of FGF signaling in mouse epiblast stem cells and human embryonic stem cells","volume":"6","author":"B Greber","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.neuron.2013.05.029","article-title":"Rapid Single-Step Induction of Functional Neurons from Human Pluripotent Stem Cells","volume":"78","author":"Y Zhang","year":"2013","journal-title":"Neuron"},{"key":"ref40","first-page":"2406","article-title":"Nat. Protoc","volume":"1","author":"S Kaech","year":"2006","journal-title":"Nat. Protoc"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1046\/j.1523-1747.2002.01744.x","article-title":"Inducible nitric oxide synthase is expressed in normal human melanocytes but not in melanoma cells in response to tumor necrosis factor-alpha, interferon-gamma, and lipopolysaccharide","volume":"118","author":"LF Fecker","year":"2002","journal-title":"J Invest Dermatol"},{"issue":"8","key":"ref42","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1111\/j.1600-0625.2009.00977.x","article-title":"Efficient and selective tumor cell lysis and induction of apoptosis in melanoma cells by a conditional replication-competent CD95L adenovirus","volume":"19","author":"LF Fecker","year":"2010","journal-title":"Exp dermatol"},{"issue":"11","key":"ref43","doi-asserted-by":"crossref","first-page":"e27352","DOI":"10.1371\/journal.pone.0027352","article-title":"Mitochondrial-associated cell death mechanisms are reset to an embryonic-like state in aged donor-derived iPS cells harboring chromosomal aberrations","volume":"6","author":"A Prigione","year":"2011","journal-title":"PLoS One"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1083\/jcb.201002108","article-title":"Regulation of the autophagy protein LC3 by phosphorylation","volume":"190","author":"III Cherra SJ","year":"2010","journal-title":"J Cell Biol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"K Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"7","DOI":"10.5045\/br.2014.49.1.7","article-title":"Disease modeling and cell based therapy with iPSC: future therapeutic option with fast and safe application","volume":"49","author":"C Kim","year":"2014","journal-title":"Blood Res"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0065-230X(08)00005-5","article-title":"The tumorigenicity of human embryonic stem cells","volume":"100","author":"B Blum","year":"2008","journal-title":"Adv Cancer Res"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.stem.2011.06.013","article-title":"Large-scale analysis reveals acquisition of lineage-specific chromosomal aberrations in human adult stem cells","volume":"9","author":"U Ben-David","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.stem.2010.07.017","article-title":"Identification and classification of chromosomal aberrations in human induced pluripotent stem cells","volume":"7","author":"Y Mayshar","year":"2010","journal-title":"Cell Stem Cell"},{"issue":"10","key":"ref50","doi-asserted-by":"crossref","first-page":"e13410","DOI":"10.1371\/journal.pone.0013410","article-title":"DNA damage responses in human induced pluripotent stem cells and embryonic stem cells","volume":"5","author":"O Momcilovic","year":"2010","journal-title":"PLoS One"},{"key":"ref51","unstructured":"Zhang WY, de Almeida PE, Wu JC. Teratoma formation: A tool for monitoring pluripotency in stem cell research. StemBook. 2008\u20132012; [Internet]"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1002\/stem.471","article-title":"Human induced pluripotent stem cells develop teratoma more efficiently and faster than human embryonic stem cells regardless the site of injection","volume":"28","author":"I Gutierrez-Aranda","year":"2010","journal-title":"Stem Cells"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s12015-009-9103-z","article-title":"Presence of a ROCK inhibitor in extracellular matrix supports more undifferentiated growth of feeder-free human embryonic and induced pluripotent stem cells upon passaging","volume":"6","author":"M Pakzad","year":"2010","journal-title":"Stem Cell Rev"},{"issue":"3","key":"ref54","doi-asserted-by":"crossref","first-page":"e33953","DOI":"10.1371\/journal.pone.0033953","article-title":"Maxadilan prevents apoptosis in iPS cells and shows no effects on the pluripotent state or karyotype","volume":"7","author":"Z Zhao","year":"2012","journal-title":"PLoS One"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.bbamcr.2010.10.017","article-title":"Bcl-2 proteins and mitochondria specificity in membrane targeting for death","volume":"1813","author":"J Lindsay","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1582-4934.2005.tb00337.x","article-title":"The activation of Akt\/PKB signaling pathway and cell survival","volume":"9","author":"G Song","year":"2005","journal-title":"J Cell Mol Med"},{"key":"ref57","first-page":"103","article-title":"Wortmannin induces MCF-7 breast cancer cell death via the apoptotic pathway, involving chromatin condensation, generation of reactive oxygen species, and membrane blebbing","volume":"4","author":"R Akter","year":"2012","journal-title":"Breast Cancer (Dove Med Press)"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/nbt.1667","article-title":"Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells","volume":"28","author":"JM Polo","year":"2010","journal-title":"Nat Biotechnol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1126\/science.1162494","article-title":"Induced pluripotent stem cells generated without viral integration","volume":"322","author":"M Stadtfeld","year":"2008","journal-title":"Science"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/ncb2239","article-title":"Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells","volume":"13","author":"Y Ohi","year":"2011","journal-title":"Nat Cell Biol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/nmeth.1699","article-title":"Proteomic and phosphoproteomic comparison of human ES and iPS cells","volume":"8","author":"DH Phanstiel","year":"2011","journal-title":"Nat Methods"},{"issue":"1","key":"ref62","doi-asserted-by":"crossref","first-page":"e30234","DOI":"10.1371\/journal.pone.0030234","article-title":"Differential coupling of self-renewal signaling pathways in murine induced pluripotent stem cells","volume":"7","author":"L Orlando","year":"2012","journal-title":"PLoS One"},{"issue":"2","key":"ref63","doi-asserted-by":"crossref","first-page":"e56399","DOI":"10.1371\/journal.pone.0056399","article-title":"The role of NF-kappaB signaling in the maintenance of pluripotency of human induced pluripotent stem cells","volume":"8","author":"O Takase","year":"2013","journal-title":"PLoS One"},{"key":"ref64","first-page":"123","article-title":"Increased Bax\/Bcl-2 ratio up-regulates caspase-3 and increases apoptosis in the thymus of patients with myasthenia gravis","volume":"21","author":"S Salakou","year":"2007","journal-title":"In Vivo"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0154770","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T15:26:34Z","timestamp":1589037994000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0154770"}},"subtitle":[],"editor":[{"given":"Eric","family":"Asselin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,5,3]]},"references-count":64,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2016,5,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0154770","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,3]]}}}