{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T20:01:59Z","timestamp":1769716919646,"version":"3.49.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":1001,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003339","name":"Consejo Superior de Investigaciones Cient\u00edficas","doi-asserted-by":"publisher","award":["BFU2011-26596"],"award-info":[{"award-number":["BFU2011-26596"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","award":["PEOPLE-2011-ITN289880"],"award-info":[{"award-number":["PEOPLE-2011-ITN289880"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["2012-StG-311736-PD-HUMMODEL"],"award-info":[{"award-number":["2012-StG-311736-PD-HUMMODEL"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministerio de Economica y Competitividad","award":["P113\/00699"],"award-info":[{"award-number":["P113\/00699"]}]},{"name":"Red de Terapia Celular","award":["TerCel RD16\/0011\/0024"],"award-info":[{"award-number":["TerCel RD16\/0011\/0024"]}]},{"DOI":"10.13039\/501100003339","name":"Consejo Superior de Investigaciones Cient\u00edficas","doi-asserted-by":"publisher","award":["BFU2011\u201026596"],"award-info":[{"award-number":["BFU2011\u201026596"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","award":["PEOPLE\u20102011\u2010ITN289880"],"award-info":[{"award-number":["PEOPLE\u20102011\u2010ITN289880"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["2012\u2010StG\u2010311736\u2010PD\u2010HUMMODEL"],"award-info":[{"award-number":["2012\u2010StG\u2010311736\u2010PD\u2010HUMMODEL"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>When considering the clinical applications of autologous cell replacement therapy of human induced pluripotent stem cells (iPSC)-derived cells, there is a clear need to better understand what the immune response will be before we embark on extensive clinical trials to treat or model human disease. We performed a detailed assessment comparing human fibroblast cell lines (termed F1) reprogrammed into human iPSC and subsequently differentiated back to fibroblast cells (termed F2) or other human iPSC-derived cells including neural stem cells (NSC) made from either retroviral, episomal, or synthetic mRNA cell reprogramming methods. Global proteomic analysis reveals the main differences in signal transduction and immune cell protein expression between F1 and F2 cells, implicating wild type (WT) toll like receptor protein 3 (TLR3). Furthermore, global methylome analysis identified an isoform of the human TLR3 gene that is not epigenetically reset correctly upon differentiation to F2 cells resulting in a hypomethylated transcription start site in the TLR3 isoform promoter and overexpression in most human iPSC-derived cells not seen in normal human tissue. The human TLR3 isoform in human iPSC-NSC functions to suppress NF-KB p65 signaling pathway in response to virus (Poly IC), suggesting suppressed immunity of iPSC-derived cells to viral infection. The sustained WT TLR3 and TLR3 isoform overexpression is central to understanding the altered immunogenicity of human iPSC-derived cells calling for screening of human iPSC-derived cells for TLR3 expression levels before applications. Stem Cells \u00a02019;37:476\u2013488<\/jats:p>\n               <jats:sec>\n                  <jats:title\/>\n               <\/jats:sec>","DOI":"10.1002\/stem.2966","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T15:46:10Z","timestamp":1546530370000},"page":"476-488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Global Proteomic and Methylome Analysis in Human Induced Pluripotent Stem Cells Reveals Overexpression of a Human TLR3 Affecting Proper Innate Immune Response Signaling"],"prefix":"10.1093","volume":"37","author":[{"given":"Jordi","family":"Requena","sequence":"first","affiliation":[{"name":"a Molecular Genetics and Control of Pluripotency Laboratory, Faculty of Medicine, Department of Biomedicine, University of Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Belen","family":"Alvarez-Palomo","sequence":"additional","affiliation":[{"name":"a Molecular Genetics and Control of Pluripotency Laboratory, Faculty of Medicine, Department of Biomedicine, University of Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montserrat","family":"Codina-Pascual","sequence":"additional","affiliation":[{"name":"b Genetics Unit, Department of Biomedicine, Faculty of Medicine, University of Barcelona, IDIBAPS and Hospital Clinic, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul","family":"Delgado-Morales","sequence":"additional","affiliation":[{"name":"c Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain"},{"name":"d Department of Psychiatry & Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Moran","sequence":"additional","affiliation":[{"name":"c Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manel","family":"Esteller","sequence":"additional","affiliation":[{"name":"c Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain"},{"name":"e Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain"},{"name":"f Instituci\u00f3 Catalana de Recerca i Estudis Avan\u00e7ats (ICREA), Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mart\u00ed","family":"Sal","sequence":"additional","affiliation":[{"name":"a Molecular Genetics and Control of Pluripotency Laboratory, Faculty of Medicine, Department of Biomedicine, University of Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manel","family":"Juan","sequence":"additional","affiliation":[{"name":"g Service of Immunology, Hospital Clinic, Hospital Sant Joan de D\u00e9u, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Boronat Barado","sequence":"additional","affiliation":[{"name":"g Service of Immunology, Hospital Clinic, Hospital Sant Joan de D\u00e9u, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Consiglio","sequence":"additional","affiliation":[{"name":"h Department of Pathology and Experimental Therapeutics, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat 08908, Spain"},{"name":"i Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona 08028, Spain"},{"name":"j Department of Molecular and Translational Medicine, University of Brescia, Brescia 25121, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orleigh Addeleccia","family":"Bogle","sequence":"additional","affiliation":[{"name":"b Genetics Unit, Department of Biomedicine, Faculty of Medicine, University of Barcelona, IDIBAPS and Hospital Clinic, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernst","family":"Wolvetang","sequence":"additional","affiliation":[{"name":"k Stem Cell Engineering Group, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Queensland, Brisbane, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry","family":"Ovchinnikov","sequence":"additional","affiliation":[{"name":"k Stem Cell Engineering Group, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Queensland, Brisbane, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inaki","family":"Alvarez","sequence":"additional","affiliation":[{"name":"l Immunology Unit, Department of Cell Biology, Physiology and Immunology and Institute of Biotechnology and Biomedicine, Autonomous University of Barcelona, Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Jaraquemada","sequence":"additional","affiliation":[{"name":"l Immunology Unit, Department of Cell Biology, Physiology and Immunology and Institute of Biotechnology and Biomedicine, Autonomous University of Barcelona, Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jovita","family":"Mezquita-Pla","sequence":"additional","affiliation":[{"name":"a Molecular Genetics and Control of Pluripotency Laboratory, Faculty of Medicine, Department of Biomedicine, University of Barcelona, Barcelona, Spain"},{"name":"e Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-2410","authenticated-orcid":false,"given":"Rafael","family":"Oliva","sequence":"additional","affiliation":[{"name":"b Genetics Unit, Department of Biomedicine, Faculty of Medicine, University of Barcelona, IDIBAPS and Hospital Clinic, Barcelona, Spain"},{"name":"e Department of Biomedicine, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5619-8680","authenticated-orcid":false,"given":"Michael J.","family":"Edel","sequence":"additional","affiliation":[{"name":"a Molecular Genetics and Control of Pluripotency Laboratory, Faculty of Medicine, Department of Biomedicine, University of Barcelona, Barcelona, Spain"},{"name":"m Department of Physiology, Anatomy and Genetics, Oxford University, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,2,14]]},"reference":[{"key":"2022022514303998300_stem2966-bib-0001","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":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"2022022514303998300_stem2966-bib-0002","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1101\/gad.1876710","article-title":"Rem2 GTPase maintains survival of human embryonic stem cells as well as enhancing reprogramming by regulating p53 and cyclin D1","volume":"24","author":"Edel","year":"2010","journal-title":"Genes Dev"},{"key":"2022022514303998300_stem2966-bib-0003","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3390\/jcm3020373","article-title":"The power and the promise of cell reprogramming: Personalized autologous body organ and cell transplantation","volume":"3","author":"Palomo","year":"2014","journal-title":"J Clin Med"},{"key":"2022022514303998300_stem2966-bib-0004","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1126\/science.284.5418.1313","article-title":"Phylogenetic perspectives in innate immunity","volume":"284","author":"Hoffmann","year":"1999","journal-title":"Science"},{"key":"2022022514303998300_stem2966-bib-0005","doi-asserted-by":"crossref","first-page":"7963","DOI":"10.4049\/jimmunol.0803864","article-title":"Cytokine modulation of TLR expression and activation in mesenchymal stromal cells leads to a proinflammatory phenotype","volume":"182","author":"Romieu-Mourez","year":"2009","journal-title":"J Immunol"},{"key":"2022022514303998300_stem2966-bib-0006","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.cellsig.2014.01.015","article-title":"TLR3 regulates mycobacterial RNA-induced IL-10 production through the PI3K\/AKT signaling pathway","volume":"26","author":"Bai","year":"2014","journal-title":"Cell Signal"},{"key":"2022022514303998300_stem2966-bib-0007","doi-asserted-by":"crossref","first-page":"e69617","DOI":"10.1371\/journal.pone.0069617","article-title":"Low immunogenicity of neural progenitor cells differentiated from induced pluripotent stem cells derived from less immunogenic somatic cells","volume":"8","author":"Liu","year":"2013","journal-title":"PLoS One"},{"key":"2022022514303998300_stem2966-bib-0008","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/nature10135","article-title":"Immunogenicity of induced pluripotent stem cells","volume":"474","author":"Zhao","year":"2011","journal-title":"Nature"},{"key":"2022022514303998300_stem2966-bib-0009","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.stem.2013.01.006","article-title":"Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells","volume":"12","author":"Guha","year":"2013","journal-title":"Cell Stem Cell"},{"key":"2022022514303998300_stem2966-bib-0010","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.stemcr.2013.08.007","article-title":"Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a nonhuman primate","volume":"1","author":"Morizane","year":"2013","journal-title":"Stem Cell Reports"},{"key":"2022022514303998300_stem2966-bib-0011","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1038\/ncomms4903","article-title":"Transplanted terminally differentiated induced pluripotent stem cells are accepted by immune mechanisms similar to self-tolerance","volume":"5","author":"Almeida","year":"2014","journal-title":"Nat Commun"},{"key":"2022022514303998300_stem2966-bib-0012","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.stem.2015.07.021","article-title":"Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells","volume":"17","author":"Zhao","year":"2015","journal-title":"Cell Stem Cell"},{"key":"2022022514303998300_stem2966-bib-0013","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nature11807","article-title":"Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells","volume":"494","author":"Araki","year":"2013","journal-title":"Nature"},{"key":"2022022514303998300_stem2966-bib-0014","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/stem.2227","article-title":"Brief report: Immune microenvironment determines the immunogenicity of induced pluripotent stem cell derivatives","volume":"34","author":"Todorova","year":"2016","journal-title":"Stem Cells"},{"key":"2022022514303998300_stem2966-bib-0015","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.3390\/jcm4061193","article-title":"The possible future roles for iPSC-derived therapy for autoimmune diseases","volume":"4","author":"Hew","year":"2015","journal-title":"J Clin Med"},{"key":"2022022514303998300_stem2966-bib-0016","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1056\/NEJMc1706274","article-title":"Autologous induced stem-cell-derived retinal cells for macular degeneration","volume":"377","author":"Mandai","year":"2017","journal-title":"N Engl J Med"},{"key":"2022022514303998300_stem2966-bib-0017","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1056\/NEJMoa1608368","article-title":"Autologous induced stem-cell-derived retinal cells for macular degeneration","volume":"376","author":"Mandai","year":"2017","journal-title":"N Engl J Med"},{"key":"2022022514303998300_stem2966-bib-0018","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.stemcr.2013.12.007","article-title":"Characterization of human induced pluripotent stem cell-derived retinal pigment epithelium cell sheets aiming for clinical application","volume":"2","author":"Kamao","year":"2014","journal-title":"Stem Cell Reports"},{"key":"2022022514303998300_stem2966-bib-0019","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13069-015-0026-9","article-title":"Prospects for clinical use of reprogrammed cells for autologous treatment of macular degeneration","volume":"8","author":"Alvarez Palomo","year":"2015","journal-title":"Fibrogenesis Tissue Repair"},{"key":"2022022514303998300_stem2966-bib-0020","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1089\/hum.2011.054","article-title":"Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery of LMX1A in human embryonic stem cells and induced pluripotent stem cells","volume":"23","author":"Sanchez-Danes","year":"2012","journal-title":"Hum Gene Ther"},{"key":"2022022514303998300_stem2966-bib-0021","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/emmm.201200215","article-title":"Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease","volume":"4","author":"Sanchez-Danes","year":"2012","journal-title":"EMBO Mol Med"},{"key":"2022022514303998300_stem2966-bib-0022","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/stem.1297","article-title":"Integration-free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology","volume":"31","author":"Briggs","year":"2013","journal-title":"Stem Cells"},{"key":"2022022514303998300_stem2966-bib-0023","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":"2022022514303998300_stem2966-bib-0024","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","article-title":"Bioconductor: Open software development for computational biology and bioinformatics","volume":"5","author":"Gentleman","year":"2004","journal-title":"Genome Biol"},{"key":"2022022514303998300_stem2966-bib-0025","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2217\/epi.09.14","article-title":"Genome-wide DNA methylation profiling using Infinium(R) assay","volume":"1","author":"Bibikova","year":"2009","journal-title":"Epigenomics"},{"key":"2022022514303998300_stem2966-bib-0026","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang da","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2022022514303998300_stem2966-bib-0027","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang da","year":"2009","journal-title":"Nat Protoc"},{"key":"2022022514303998300_stem2966-bib-0028","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2022022514303998300_stem2966-bib-0029","doi-asserted-by":"crossref","first-page":"e7475","DOI":"10.1371\/journal.pone.0007475","article-title":"Identification of markers that distinguish monocyte-derived fibrocytes from monocytes, macrophages, and fibroblasts","volume":"4","author":"Pilling","year":"2009","journal-title":"PLoS One"},{"key":"2022022514303998300_stem2966-bib-0030","doi-asserted-by":"crossref","first-page":"9864","DOI":"10.1073\/pnas.142298299","article-title":"Characterization of the expression of MHC proteins in human embryonic stem cells","volume":"99","author":"Drukker","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022022514303998300_stem2966-bib-0031","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jneuroim.2004.09.009","article-title":"Preferential expression and function of Toll-like receptor 3 in human astrocytes","volume":"159","author":"Farina","year":"2005","journal-title":"J Neuroimmunol"},{"key":"2022022514303998300_stem2966-bib-0032","doi-asserted-by":"crossref","first-page":"696","DOI":"10.5483\/BMBRep.2015.48.12.106","article-title":"An inhibitory alternative splice isoform of Toll-like receptor 3 is induced by type I interferons in human astrocyte cell lines","volume":"48","author":"Seo","year":"2015","journal-title":"BMB Rep"},{"key":"2022022514303998300_stem2966-bib-0033","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3349\/ymj.2004.45.2.359","article-title":"Cloning of TLR3 isoform","volume":"45","author":"Yang","year":"2004","journal-title":"Yonsei Med J"},{"key":"2022022514303998300_stem2966-bib-0034","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s11427-013-4598-6","article-title":"Neural progenitor cells from human induced pluripotent stem cells generated less autogenous immune response","volume":"57","author":"Huang","year":"2014","journal-title":"Sci China Life Sci"},{"key":"2022022514303998300_stem2966-bib-0035","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/nsmb847","article-title":"Novel roles of TLR3 tyrosine phosphorylation and PI3 kinase in double-stranded RNA signaling","volume":"11","author":"Sarkar","year":"2004","journal-title":"Nat Struct Mol Biol"},{"key":"2022022514303998300_stem2966-bib-0036","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nature19834","article-title":"PI3Kgamma is a molecular switch that controls immune suppression","volume":"539","author":"Kaneda","year":"2016","journal-title":"Nature"},{"key":"2022022514303998300_stem2966-bib-0037","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nature11583","article-title":"Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells","volume":"491","author":"Lafaille","year":"2012","journal-title":"Nature"},{"key":"2022022514303998300_stem2966-bib-0038","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.cell.2012.09.034","article-title":"Activation of innate immunity is required for efficient nuclear reprogramming","volume":"151","author":"Lee","year":"2012","journal-title":"Cell"}],"container-title":["Stem Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fstem.2966","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/stem.2966","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/stem.2966","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/37\/4\/476\/42611504\/stmcls_37_4_476.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/37\/4\/476\/42611504\/stmcls_37_4_476.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T14:37:36Z","timestamp":1645799856000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stmcls\/article\/37\/4\/476\/6408975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,14]]},"references-count":38,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,2,14]]},"published-print":{"date-parts":[[2019,4,1]]}},"URL":"https:\/\/doi.org\/10.1002\/stem.2966","relation":{},"ISSN":["1066-5099","1549-4918"],"issn-type":[{"value":"1066-5099","type":"print"},{"value":"1549-4918","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,4,1]]},"published":{"date-parts":[[2019,2,14]]},"assertion":[{"value":"2018-09-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}