{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:15:56Z","timestamp":1790144156561,"version":"4.0.1"},"reference-count":41,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T00:00:00Z","timestamp":1576627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009425","name":"Landsteiner Foundation for Blood Transfusion Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009425","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Stem Cell Reports"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1016\/j.stemcr.2019.12.010","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T10:39:17Z","timestamp":1579171157000},"page":"300-311","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"title":["iPSC-Based Modeling of RAG2 Severe Combined Immunodeficiency Reveals Multiple T Cell Developmental Arrests"],"prefix":"10.1016","volume":"14","author":[{"given":"Maria","family":"Themeli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amiet","family":"Chhatta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester","family":"Boersma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk Jan","family":"Prins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"Cordes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"de Wilt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A\u00efda Shahrabi","family":"Farahani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Vandekerckhove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"van der Burg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rob C.","family":"Hoeben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.T.","family":"Staal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald M.M.","family":"Mikkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.stemcr.2019.12.010_bib1","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1182\/blood.V93.9.3033.409k39_3033_3043","article-title":"TCR gene rearrangements and expression of the pre-T cell receptor complex during human T-cell differentiation","volume":"93","author":"Blom","year":"1999","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.12.010_bib2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1182\/blood-2015-10-676304","article-title":"Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies","volume":"128","author":"Brauer","year":"2016","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.12.010_bib3","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/sj.leu.2403263","article-title":"Rearranged T-cell receptor beta genes represent powerful targets for quantification of minimal residual disease in childhood and adult T-cell acute lymphoblastic leukemia","volume":"18","author":"Bruggemann","year":"2004","journal-title":"Leukemia"},{"key":"10.1016\/j.stemcr.2019.12.010_bib4","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.celrep.2015.08.013","article-title":"Modeling human severe combined immunodeficiency and correction by CRISPR\/Cas9-Enhanced gene targeting","volume":"12","author":"Chang","year":"2015","journal-title":"Cell Rep."},{"key":"10.1016\/j.stemcr.2019.12.010_bib5","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41467-017-00687-1","article-title":"In trans paired nicking triggers seamless genome editing without double-stranded DNA cutting","volume":"8","author":"Chen","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.stemcr.2019.12.010_bib6","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aao2966","article-title":"Human thymopoiesis is influenced by a common genetic variant within the TCRA-TCRD locus","volume":"10","author":"Clave","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.stemcr.2019.12.010_bib7","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.diff.2013.01.001","article-title":"Polycistronic lentivirus induced pluripotent stem cells from skin biopsies after long term storage, blood outgrowth endothelial cells and cells from milk teeth","volume":"85","author":"Dambrot","year":"2013","journal-title":"Differentiation"},{"key":"10.1016\/j.stemcr.2019.12.010_bib8","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1084\/jem.20042524","article-title":"New insights on human T\u00a0cell development by quantitative T\u00a0cell receptor gene rearrangement studies and gene expression profiling","volume":"201","author":"Dik","year":"2005","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.stemcr.2019.12.010_bib9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ymeth.2015.10.001","article-title":"Directed differentiation of definitive hemogenic endothelium and hematopoietic progenitors from human pluripotent stem cells","volume":"101","author":"Ditadi","year":"2016","journal-title":"Methods"},{"key":"10.1016\/j.stemcr.2019.12.010_bib10","doi-asserted-by":"crossref","first-page":"798","DOI":"10.3389\/fimmu.2017.00798","article-title":"Natural killer cells from patients with recombinase-activating gene and non-homologous end joining gene defects comprise a higher frequency of CD56(bright) NKG2A(+++) cells, and yet display increased degranulation and higher perforin content","volume":"8","author":"Dobbs","year":"2017","journal-title":"Front Immunol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.iac.2009.10.004","article-title":"Radiosensitive severe combined immunodeficiency disease","volume":"30","author":"Dvorak","year":"2010","journal-title":"Immunol. Allergy Clin. North Am."},{"key":"10.1016\/j.stemcr.2019.12.010_bib12","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1046\/j.1365-2249.2000.01359.x","article-title":"Severe combined immunodeficiencies (SCID)","volume":"122","author":"Fischer","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib13","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.4049\/jimmunol.175.4.2495","article-title":"Lymphoid differentiation pathways can be traced by TCR delta rearrangements","volume":"175","author":"Fronkova","year":"2005","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib14","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1634\/stemcells.2008-0813","article-title":"Generation of T lineage cells from human embryonic stem cells in a feeder free system","volume":"27","author":"Galic","year":"2009","journal-title":"Stem Cells"},{"key":"10.1016\/j.stemcr.2019.12.010_bib15","doi-asserted-by":"crossref","first-page":"3749","DOI":"10.1182\/blood-2013-02-380105","article-title":"How I treat severe combined immunodeficiency","volume":"122","author":"Gaspar","year":"2013","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.12.010_bib41","doi-asserted-by":"crossref","first-page":"e3084","DOI":"10.1371\/journal.pone.0003084","article-title":"Targeted chromosomal insertion of large DNA into the human genome by a fiber-modified high-capacity adenovirus-based vector system","volume":"3","author":"Gon\u00e7alves","year":"2008","journal-title":"PLoS One"},{"key":"10.1016\/j.stemcr.2019.12.010_bib16","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1182\/blood-2007-08-106294","article-title":"Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7- lympho-myeloid thymic progenitors","volume":"111","author":"Hao","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.12.010_bib17","doi-asserted-by":"crossref","first-page":"12538","DOI":"10.1073\/pnas.1209979109","article-title":"Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells","volume":"109","author":"Kajiwara","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.stemcr.2019.12.010_bib18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.cell.2014.08.026","article-title":"The RAG recombinase dictates functional heterogeneity and cellular fitness in natural killer cells","volume":"159","author":"Karo","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.stemcr.2019.12.010_bib19","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nature22403","article-title":"Common genetic variation drives molecular heterogeneity in human iPSCs","volume":"546","author":"Kilpinen","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.stemcr.2019.12.010_bib20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.stemcr.2016.06.003","article-title":"Gene correction of iPSCs from a Wiskott-Aldrich syndrome patient normalizes the lymphoid developmental and functional defects","volume":"7","author":"Laskowski","year":"2016","journal-title":"Stem Cell Reports"},{"key":"10.1016\/j.stemcr.2019.12.010_bib21","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1097\/MOH.0000000000000239","article-title":"Endothelial functions of platelet\/endothelial cell adhesion molecule-1 (CD31)","volume":"23","author":"Lertkiatmongkol","year":"2016","journal-title":"Curr. Opin. Hematol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib22","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0092-8674(02)00671-2","article-title":"Hairpin opening and overhang processing by an Artemis\/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination","volume":"108","author":"Ma","year":"2002","journal-title":"Cell"},{"key":"10.1016\/j.stemcr.2019.12.010_bib23","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.stem.2015.02.005","article-title":"Lymphoid regeneration from gene-corrected SCID-X1 subject-derived iPSCs","volume":"16","author":"Menon","year":"2015","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.stemcr.2019.12.010_bib24","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1097\/CJI.0b013e3181cd872d","article-title":"IL-7 enhances survival of human CD56bright NK cells","volume":"33","author":"Michaud","year":"2010","journal-title":"J.\u00a0Immunother."},{"key":"10.1016\/j.stemcr.2019.12.010_bib25","doi-asserted-by":"crossref","first-page":"4823","DOI":"10.1182\/blood-2009-04-216374","article-title":"Functionally distinct subsets of human NK cells and monocyte\/DC-like cells identified by coexpression of CD56, CD7, and CD4","volume":"114","author":"Milush","year":"2009","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.12.010_bib26","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/intimm\/dxr035","article-title":"The 'T-cell-ness' of NK cells: unexpected similarities between NK cells and T\u00a0cells","volume":"23","author":"Narni-Mancinelli","year":"2011","journal-title":"Int. Immunol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib27","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nri.2016.28","article-title":"Human RAG mutations: biochemistry and clinical implications","volume":"16","author":"Notarangelo","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib28","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/0092-8674(92)90029-C","article-title":"RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement","volume":"68","author":"Shinkai","year":"1992","journal-title":"Cell"},{"key":"10.1016\/j.stemcr.2019.12.010_bib29","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.bcmd.2011.04.001","article-title":"Cytokines and culture medium have a major impact on human in\u00a0vitro T-cell differentiation","volume":"47","author":"Six","year":"2011","journal-title":"Blood Cells Mol Dis"},{"key":"10.1016\/j.stemcr.2019.12.010_bib30","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":"10.1016\/j.stemcr.2019.12.010_bib31","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1038\/nbt.2678","article-title":"Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy","volume":"31","author":"Themeli","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib32","doi-asserted-by":"crossref","first-page":"6879","DOI":"10.4049\/jimmunol.0803670","article-title":"Generation of T\u00a0cells from human embryonic stem cell-derived hematopoietic zones","volume":"182","author":"Timmermans","year":"2009","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib33","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1182\/blood-2004-04-1649","article-title":"Human embryonic stem cell-derived CD34+ cells: efficient production in the coculture with OP9 stromal cells and analysis of lymphohematopoietic potential","volume":"105","author":"Vodyanik","year":"2005","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.12.010_bib34","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/ni1395","article-title":"A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127","volume":"7","author":"Vosshenrich","year":"2006","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib35","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/mt.2010.314","article-title":"Lentiviral vector design and imaging approaches to visualize the early stages of cellular reprogramming","volume":"19","author":"Warlich","year":"2011","journal-title":"Mol. Ther."},{"key":"10.1016\/j.stemcr.2019.12.010_bib36","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.1182\/blood-2005-08-3412","article-title":"Human thymus contains multipotent progenitors with T\/B lymphoid, myeloid, and erythroid lineage potential","volume":"107","author":"Weerkamp","year":"2006","journal-title":"Blood"},{"key":"10.1016\/j.stemcr.2019.12.010_bib37","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.jaci.2015.08.022","article-title":"Identification of checkpoints in human T-cell development using severe combined immunodeficiency stem cells","volume":"137","author":"Wiekmeijer","year":"2016","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib38","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.it.2013.07.005","article-title":"Location and cellular stages of natural killer cell development","volume":"34","author":"Yu","year":"2013","journal-title":"Trends Immunol."},{"key":"10.1016\/j.stemcr.2019.12.010_bib39","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced pluripotent stem cell lines derived from human somatic cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.stemcr.2019.12.010_bib40","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1016\/j.stemcr.2017.10.020","article-title":"Generation of \"Off-the-Shelf\" natural killer cells from peripheral blood cell-derived induced pluripotent stem cells","volume":"9","author":"Zeng","year":"2017","journal-title":"Stem Cell Reports"}],"container-title":["Stem Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213671119304497?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213671119304497?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T09:44:05Z","timestamp":1761990245000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213671119304497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["S2213671119304497"],"URL":"https:\/\/doi.org\/10.1016\/j.stemcr.2019.12.010","relation":{},"ISSN":["2213-6711"],"issn-type":[{"value":"2213-6711","type":"print"}],"subject":[],"published":{"date-parts":[[2020,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"iPSC-Based Modeling of RAG2 Severe Combined Immunodeficiency Reveals Multiple T Cell Developmental Arrests","name":"articletitle","label":"Article Title"},{"value":"Stem Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.stemcr.2019.12.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 The Authors.","name":"copyright","label":"Copyright"}]}}