{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:30:40Z","timestamp":1790512240525,"version":"4.1.0"},"reference-count":167,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001279","name":"Great Ormond Street Hospital Charity","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001279","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Inborn errors of thymic stromal cell development and function lead to impaired T-cell development resulting in a susceptibility to opportunistic infections and autoimmunity. In their most severe form, congenital athymia, these disorders are life-threatening if left untreated. Athymia is rare and is typically associated with complete DiGeorge syndrome, which has multiple genetic and environmental etiologies. It is also found in rare cases of T-cell lymphopenia due to Nude SCID and Otofaciocervical Syndrome type 2, or in the context of genetically undefined defects. This group of disorders cannot be corrected by hematopoietic stem cell transplantation, but upon timely recognition as thymic defects, can successfully be treated by thymus transplantation using cultured postnatal thymic tissue with the generation of na\u00efve T-cells showing a diverse repertoire. Mortality after this treatment usually occurs before immune reconstitution and is mainly associated with infections most often acquired pre-transplantation. In this review, we will discuss the current approaches to the diagnosis and management of thymic stromal cell defects, in particular those resulting in athymia. We will discuss the impact of the expanding implementation of newborn screening for T-cell lymphopenia, in combination with next generation sequencing, as well as the role of novel diagnostic tools distinguishing between hematopoietic and thymic stromal cell defects in facilitating the early consideration for thymus transplantation of an increasing number of patients and disorders. Immune reconstitution after the current treatment is usually incomplete with relatively common inflammatory and autoimmune complications, emphasizing the importance for improving strategies for thymus replacement therapy by optimizing the current use of postnatal thymus tissue and developing new approaches using engineered thymus tissue.<\/jats:p>","DOI":"10.3389\/fimmu.2021.655354","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T05:01:10Z","timestamp":1616043670000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":48,"title":["Current and Future Therapeutic Approaches for Thymic Stromal Cell Defects"],"prefix":"10.3389","volume":"12","author":[{"given":"Alexandra Y.","family":"Kreins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Bonfanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Graham","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-275966","article-title":"Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly","volume":"116","author":"Janda","year":"2010","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.08.048","article-title":"Long-term results of bone marrow transplantation in complete DiGeorge syndrome","volume":"120","author":"Land","year":"2007","journal-title":"J Allergy Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195709122571102","article-title":"Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy","volume":"257","author":"Thomas","year":"1957","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103949","article-title":"Supralethal whole body irradiation and isologous marrow transplantation in man","volume":"38","author":"Thomas","year":"1959","journal-title":"J Clin Invest"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5355.459","article-title":"Role of the Thymus in Immunity","volume":"2","author":"Miller","year":"1963","journal-title":"Br Med J"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(70)92755-8","article-title":"Establishment of immunological competence in a child with congenital thymic aplasia by a graft of fetal thymus","volume":"1","author":"August","year":"1970","journal-title":"Lancet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(68)91694-2","article-title":"Foetal thymic transplant in a case of Digeorge\u2019s syndrome","volume":"2","author":"Cleveland","year":"1968","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/0090-1229(79)90130-2","article-title":"Failure of immunologic reconstitution in a patient with the DiGeorge syndrome after fetal thymus transplantation","volume":"14","author":"Pahwa","year":"1979","journal-title":"Clin Immunol Immunopathol"},{"key":"B9","doi-asserted-by":"crossref","first-page":"998","DOI":"10.4049\/jimmunol.158.2.998","article-title":"Successful formation of a chimeric human thymus allograft following transplantation of cultured postnatal human thymus","volume":"158","author":"Markert","year":"1997","journal-title":"J Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-048652","article-title":"Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants","volume":"109","author":"Markert","year":"2007","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.02.007","article-title":"Thymus transplantation","volume":"135","author":"Markert","year":"2010","journal-title":"Clin Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.03.020","article-title":"Thymus transplantation for complete DiGeorge syndrome: European experience","volume":"140","author":"Davies","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2001.19910133.x","article-title":"The development and evolution of the pharyngeal arches","volume":"199","author":"Graham","year":"2001","journal-title":"J Anat"},{"key":"B14","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/2041-9139-3-24","article-title":"Developmental and evolutionary origins of the pharyngeal apparatus","volume":"3","author":"Graham","year":"2012","journal-title":"Evodevo"},{"key":"B15","article-title":"Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos","volume":"34","author":"Le Lievre","year":"1975","journal-title":"J Embryol Exp Morphol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(01)00333-1","article-title":"Gcm2 and Foxn1 mark early parathyroid- and thymus-specific domains in the developing third pharyngeal pouch","volume":"103","author":"Gordon","year":"2001","journal-title":"Mech Dev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)80118-9","article-title":"Pharyngeal arch patterning in the absence of neural crest","volume":"9","author":"Veitch","year":"1999","journal-title":"Curr Biol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1242\/dev.059998","article-title":"Mechanisms of thymus organogenesis and morphogenesis","volume":"138","author":"Gordon","year":"2011","journal-title":"Development"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S1877-1173(10)92005-X","article-title":"Transcriptional regulation of thymus organogenesis and thymic epithelial cell differentiation","volume":"92","author":"Manley","year":"2010","journal-title":"Prog Mol Biol Transl Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545814","article-title":"FOXN1 in thymus organogenesis and development","volume":"46","author":"Vaidya","year":"2016","journal-title":"Eur J Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1242\/dev.103614","article-title":"Regeneration of the aged thymus by a single transcription factor","volume":"141","author":"Bredenkamp","year":"2014","journal-title":"Development"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-156265","article-title":"Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner","volume":"113","author":"Chen","year":"2009","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1242\/dev.087320","article-title":"Dynamics of thymus organogenesis and colonization in early human development","volume":"140","author":"Farley","year":"2013","journal-title":"Development"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.02.004","article-title":"Identification of the niche and phenotype of the first human hematopoietic stem cells","volume":"2","author":"Ivanovs","year":"2014","journal-title":"Stem Cell Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0228-6","article-title":"Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing","volume":"29","author":"Zeng","year":"2019","journal-title":"Cell Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/j.immuni.2019.09.008","article-title":"Single-Cell RNA Sequencing Resolves Spatiotemporal Development of Pre-thymic Lymphoid Progenitors and Thymus Organogenesis in Human Embryos","volume":"51","author":"Zeng","year":"2019","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-272625","article-title":"VE-cadherin expression allows identification of a new class of hematopoietic stem cells within human embryonic liver","volume":"116","author":"Oberlin","year":"2010","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nri1781","article-title":"Journey through the thymus: stromal guides for T-cell development and selection","volume":"6","author":"Takahama","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.03.005","article-title":"Thymic epithelial cells: working class heroes for T cell development and repertoire selection","volume":"33","author":"Anderson","year":"2012","journal-title":"Trends Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1016\/j.immuni.2018.04.015","article-title":"A Single-Cell Transcriptomic Atlas of Thymus Organogenesis Resolves Cell Types and Developmental Maturation","volume":"48","author":"Kernfeld","year":"2018","journal-title":"Immunity"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1101\/2020.01.28.911115","article-title":"A cell atlas of human thymic development defines T cell repertoire formation","volume":"367","author":"Park","year":"2020","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121798","article-title":"Specific Notch receptor-ligand interactions control human TCR-alphabeta\/gammadelta development by inducing differential Notch signal strength","volume":"210","author":"Van de Walle","year":"2013","journal-title":"J Exp Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1016\/j.immuni.2020.03.019","article-title":"Integrated scRNA-Seq Identifies Human Postnatal Thymus Seeding Progenitors and Regulatory Dynamics of Differentiating Immature Thymocytes","volume":"52","author":"Lavaert","year":"2020","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2019-0030","article-title":"Long-term survival and differentiation of human thymocytes in human thymus-grafted immunodeficient mice","volume":"11","author":"Tang","year":"2019","journal-title":"Immunotherapy"},{"key":"B35","doi-asserted-by":"publisher","first-page":"6372","DOI":"10.1038\/s41467-020-20082-7","article-title":"Reconstitution of a functional human thymus by postnatal stromal progenitor cells and natural whole-organ scaffolds","volume":"11","author":"Campinoti","year":"2020","journal-title":"Nat Commun"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/s41467-021-21346-6","article-title":"Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla","volume":"12","author":"Bautista","year":"2021","journal-title":"Nat Commun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nature04813","article-title":"Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium","volume":"441","author":"Rossi","year":"2006","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.07.005","article-title":"Adult thymus contains FoxN1(-) epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages","volume":"41","author":"Ucar","year":"2014","journal-title":"Immunity"},{"key":"B39","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1146\/annurev-immunol-051116-052320","article-title":"Thymic Epithelial Cells","volume":"35","author":"Abramson","year":"2017","journal-title":"Annu Rev Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4161\/cam.4.3.11789","article-title":"The thymus microenvironment in regulating thymocyte differentiation","volume":"4","author":"Gameiro","year":"2010","journal-title":"Cell Adh Migr"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1607-2","article-title":"Tracking migration during human T cell development","volume":"71","author":"Halkias","year":"2014","journal-title":"Cell Mol Life Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1003455","article-title":"Molecular mechanisms governing thymocyte migration: combined role of chemokines and extracellular matrix","volume":"75","author":"Savino","year":"2004","journal-title":"J Leukoc Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nri913","article-title":"Development of alphabeta T cells in the human thymus","volume":"2","author":"Spits","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1543","article-title":"Human alpha beta and gamma delta thymocyte development: TCR gene rearrangements, intracellular TCR beta expression, and gamma delta developmental potential\u2013differences between men and mice","volume":"176","author":"Joachims","year":"2006","journal-title":"J Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/82_2012_230","article-title":"Notch signaling during human T cell development","volume":"360","author":"Taghon","year":"2012","journal-title":"Curr Top Microbiol Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"FSO186","DOI":"10.4155\/fsoa-2016-0095","article-title":"The development of T cells from stem cells in mice and humans","volume":"3","author":"Famili","year":"2017","journal-title":"Future Sci OA"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00474-0","article-title":"Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro","volume":"17","author":"Schmitt","year":"2002","journal-title":"Immunity"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2004.08.007","article-title":"Human bone marrow CD34+ progenitor cells mature to T cells on OP9-DL1 stromal cell line without thymus microenvironment","volume":"33","author":"De Smedt","year":"2004","journal-title":"Blood Cells Mol Dis"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2011.04.001","article-title":"Cytokines and culture medium have a major impact on human in vitro T-cell differentiation","volume":"47","author":"Six","year":"2011","journal-title":"Blood Cells Mol Dis"},{"key":"B50","doi-asserted-by":"publisher","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":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.12.010","article-title":"iPSC-Based Modeling of RAG2 Severe Combined Immunodeficiency Reveals Multiple T Cell Developmental Arrests","volume":"14","author":"Themeli","year":"2020","journal-title":"Stem Cell Rep"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002957","article-title":"Artificial thymic organoids represent a reliable tool to study T-cell differentiation in patients with severe T-cell lymphopenia","volume":"4","author":"Bosticardo","year":"2020","journal-title":"Blood Adv"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.10.6477","article-title":"Human lymphoid and myeloid cell development in NOD\/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells","volume":"174","author":"Shultz","year":"2005","journal-title":"J\u00a0Immunol"},{"key":"B54","doi-asserted-by":"publisher","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":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.09.005","article-title":"Thymocyte-thymocyte interaction for efficient positive selection and maturation of CD4 T cells","volume":"23","author":"Choi","year":"2005","journal-title":"Immunity"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.09.002","article-title":"An alternate pathway for CD4 T cell development: thymocyte-expressed MHC class II selects a distinct T cell population","volume":"23","author":"Li","year":"2005","journal-title":"Immunity"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/364642a0","article-title":"Positive selection of T lymphocytes on fibroblasts","volume":"364","author":"Pawlowski","year":"1993","journal-title":"Nature"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.21.10335","article-title":"Fibroblasts can induce thymocyte positive selection in vivo","volume":"90","author":"Hugo","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.9.4945","article-title":"The role of fibroblasts in thymocyte-positive selection","volume":"169","author":"Lilic","year":"2002","journal-title":"J Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606707103","article-title":"Functional CD8+ but not CD4+ T cell responses develop independent of thymic epithelial MHC","volume":"103","author":"Martinic","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080866","article-title":"Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla","volume":"205","author":"McCaughtry","year":"2008","journal-title":"J\u00a0Exp Med"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121458","article-title":"Helios marks strongly autoreactive CD4+ T cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-kappaB","volume":"210","author":"Daley","year":"2013","journal-title":"J Exp Med"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0756-8","article-title":"Fibroblasts as a source of self-antigens for central immune tolerance","volume":"21","author":"Nitta","year":"2020","journal-title":"Nat Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00322","article-title":"Immunodeficiency in DiGeorge Syndrome and Options for Treating Cases with Complete Athymia","volume":"4","author":"Davies","year":"2013","journal-title":"Front Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy146","article-title":"Functional variants in TBX2 are associated with a syndromic cardiovascular and skeletal developmental disorder","volume":"27","author":"Liu","year":"2018","journal-title":"Hum Mol Genet"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-06-292490","article-title":"First use of thymus transplantation therapy for FOXN1 deficiency (nude\/SCID): a report of 2 cases","volume":"117","author":"Markert","year":"2011","journal-title":"Blood"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-021-00967-y","article-title":"Expanding the Nude SCID\/CID phenotype associated to FOXN1 homozygous, compound heterozygous or heterozygous mutations","author":"Giardino","year":"2021","journal-title":"J Clin Immunol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"e37042","DOI":"10.1371\/journal.pone.0037042","article-title":"Human FOXN1-deficiency is associated with alphabeta double-negative and FoxP3+ T-cell expansions that are distinctly modulated upon thymic transplantation","volume":"7","author":"Albuquerque","year":"2012","journal-title":"PLoS One"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2017.02.025","article-title":"A case of atypical, complete DiGeorge syndrome without 22q11 mutation","volume":"118","author":"Stone","year":"2017","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-015-0171-3","article-title":"Disseminated Mycobacterium kansasii disease in complete DiGeorge syndrome","volume":"35","author":"Yin","year":"2015","journal-title":"J Clin Immunol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0000000000000219","article-title":"Clinical course and outcome predictors of critically ill infants with complete DiGeorge anomaly following thymus transplantation","volume":"15","author":"Lee","year":"2014","journal-title":"Pediatr Crit Care Med"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2009.02090.x","article-title":"Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I","volume":"265","author":"Husebye","year":"2009","journal-title":"J Intern Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12714","article-title":"Lessons from primary immunodeficiencies: Autoimmune regulator and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"287","author":"Constantine","year":"2019","journal-title":"Immunol Rev"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.88782","article-title":"Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"1","author":"Ferre","year":"2016","journal-title":"JCI Insight"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav5597","article-title":"Lymphocyte-driven regional immunopathology in pneumonitis caused by impaired central immune tolerance","volume":"11","author":"Ferre","year":"2019","journal-title":"Sci Transl Med"},{"key":"B76","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.coi.2016.07.003","article-title":"AIRE-mutations and autoimmune disease","volume":"43","author":"Bruserud","year":"2016","journal-title":"Curr Opin Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2016.06.002","article-title":"AIRE genetic variants and predisposition to polygenic autoimmune disease: The case of Graves\u2019 disease and a systematic literature review","volume":"77","author":"Colobran","year":"2016","journal-title":"Hum Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-211029","article-title":"Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome","volume":"114","author":"Poliani","year":"2009","journal-title":"Blood"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-267583","article-title":"Hypomorphic Rag mutations can cause destructive midline granulomatous disease","volume":"116","author":"De Ravin","year":"2010","journal-title":"Blood"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200523087","article-title":"AIRE deficiency in thymus of 2 patients with Omenn syndrome","volume":"115","author":"Cavadini","year":"2005","journal-title":"J Clin Invest"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.jaci.2015.01.040","article-title":"PRKDC mutations associated with immunodeficiency, granuloma, and autoimmune regulator-dependent autoimmunity","volume":"135","author":"Mathieu","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/imr.12033","article-title":"NF-kappaB: roles and regulation in different CD4(+) T-cell subsets","volume":"252","author":"Oh","year":"2013","journal-title":"Immunol Rev"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.09.009","article-title":"Germline mutations in NFKB2 implicate the noncanonical NF-kappaB pathway in the pathogenesis of common variable immunodeficiency","volume":"93","author":"Chen","year":"2013","journal-title":"Am J Hum Genet"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00297","article-title":"Clinical and Immunological Phenotype of Patients With Primary Immunodeficiency Due to Damaging Mutations in NFKB2","volume":"10","author":"Klemann","year":"2019","journal-title":"Front Immunol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-06-578542","article-title":"Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100","volume":"124","author":"Lee","year":"2014","journal-title":"Blood"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.52","article-title":"The non-canonical NF-kappaB pathway in immunity and inflammation","volume":"17","author":"Sun","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200476","article-title":"Nfkb2 variants reveal a p100-degradation threshold that defines autoimmune susceptibility","volume":"218","author":"Wirasinha","year":"2021","journal-title":"J Exp Med"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1016\/j.jaci.2014.07.019","article-title":"Immune deficiency-related enteropathy-lymphocytopenia-alopecia syndrome results from tetratricopeptide repeat domain 7A deficiency","volume":"134","author":"Lemoine","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.jaci.2013.06.013","article-title":"Whole-exome sequencing identifies tetratricopeptide repeat domain 7A (TTC7A) mutations for combined immunodeficiency with intestinal atresias","volume":"132","author":"Chen","year":"2013","journal-title":"J\u00a0Allergy Clin Immunol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-696385","article-title":"Stem cell transplantation for tetratricopeptide repeat domain 7A deficiency: long-term follow-up","volume":"128","author":"Kammermeier","year":"2016","journal-title":"Blood"},{"key":"B91","doi-asserted-by":"publisher","first-page":"15071","DOI":"10.1038\/nrdp.2015.71","article-title":"22q11.2 deletion syndrome","volume":"1","author":"McDonald-McGinn","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2018885244","article-title":"Clinical and immunological features in a cohort of patients with partial DiGeorge syndrome followed at a single center","volume":"133","author":"Giardino","year":"2019","journal-title":"Blood"},{"key":"B93","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s10875-020-00758-x","article-title":"Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification","volume":"40","author":"Bousfiha","year":"2020","journal-title":"J Clin Immunol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1111\/j.1365-2249.2008.03681.x","article-title":"Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome","volume":"153","author":"Gennery","year":"2008","journal-title":"Clin Exp Immunol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.01.766","article-title":"Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases","volume":"113","author":"Markert","year":"2004","journal-title":"J Allergy Clin Immunol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1136\/jmg.33.8.719","article-title":"Prevalence of 22q11 microdeletion","volume":"33","author":"Tezenas Du Montcel","year":"1996","journal-title":"J Med Genet"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.9.789-a","article-title":"The annual incidence of DiGeorge\/velocardiofacial syndrome","volume":"35","author":"Devriendt","year":"1998","journal-title":"J Med Genet"},{"key":"B98","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1136\/jmg.34.10.798","article-title":"Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study","volume":"34","author":"Ryan","year":"1997","journal-title":"J Med Genet"},{"key":"B99","doi-asserted-by":"publisher","first-page":"11688","DOI":"10.1038\/ncomms11688","article-title":"Rebalancing gene haploinsufficiency in vivo by targeting chromatin","volume":"7","author":"Fulcoli","year":"2016","journal-title":"Nat Commun"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.01365","article-title":"The Genetics and Epigenetics of 22q11.2 Deletion Syndrome","volume":"10","author":"Du","year":"2019","journal-title":"Front Genet"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1038\/ng1407","article-title":"Mutations in a new member of the chromodomain gene family cause CHARGE syndrome","volume":"36","author":"Vissers","year":"2004","journal-title":"Nat Genet"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22086","article-title":"Mutation update on the CHD7 gene involved in CHARGE syndrome","volume":"33","author":"Janssen","year":"2012","journal-title":"Hum Mutat"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30560","article-title":"An epidemiological analysis of CHARGE syndrome: preliminary results from a Canadian study","author":"Issekutz","year":"2005","journal-title":"Am J Med Genet A"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.087106","article-title":"CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype","volume":"48","author":"Bergman","year":"2011","journal-title":"J Med Genet"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.215319","article-title":"DiGeorge syndrome, Tbx1, and retinoic acid signaling come full circle","volume":"106","author":"Yutzey","year":"2010","journal-title":"Circ Res"},{"key":"B106","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/ajmg.1320250614","article-title":"Fetal alcohol syndrome and DiGeorge anomaly: critical ethanol exposure periods for craniofacial malformations as illustrated in an animal model","volume":"2","author":"Sulik","year":"1986","journal-title":"Am J Med Genet Suppl"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14632-6","article-title":"Role of TBX1 in human del22q11.2 syndrome","volume":"362","author":"Yagi","year":"2003","journal-title":"Lancet"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1297\/cpe.27.159","article-title":"Novel heterozygous mutation in TBX1 in an infant with hypocalcemic seizures","volume":"27","author":"Hasegawa","year":"2018","journal-title":"Clin Pediatr Endocrinol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1038\/ng0896-458","article-title":"A common region of 10p deleted in DiGeorge and velocardiofacial syndromes","volume":"13","author":"Daw","year":"1996","journal-title":"Nat Genet"},{"key":"B110","first-page":"59","article-title":"The phenotypic spectrum of the 10p deletion syndrome versus the classical DiGeorge syndrome","volume":"10","author":"Van Esch","year":"1999","journal-title":"Genet Couns"},{"key":"B111","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.jaci.2019.09.020","article-title":"Recurrent microdeletions at chromosome 2p11.2 are associated with thymic hypoplasia and features resembling DiGeorge syndrome","volume":"145","author":"Bernstock","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1038\/18997","article-title":"Exposing the human nude phenotype","volume":"398","author":"Frank","year":"1999","journal-title":"Nature"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00187","article-title":"FOXN1: A Master Regulator Gene of Thymic Epithelial Development Program","volume":"4","author":"Romano","year":"2013","journal-title":"Front Immunol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19961016)65:2<167::AID-AJMG17>3.0.CO;2-O","article-title":"Congenital Alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs","volume":"65","author":"Pignata","year":"1996","journal-title":"Am J Med Genet"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1046\/j.1529-8817.2004.00091.x","article-title":"Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population","volume":"68","author":"Adriani","year":"2004","journal-title":"Ann Hum Genet"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2014.08.005","article-title":"A novel mutation in FOXN1 resulting in SCID: a case report and literature review","volume":"155","author":"Chou","year":"2014","journal-title":"Clin Immunol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.4.880","article-title":"Human equivalent of the mouse Nude\/SCID phenotype: long-term evaluation of immunologic reconstitution after bone marrow transplantation","volume":"97","author":"Pignata","year":"2001","journal-title":"Blood"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.06.033","article-title":"FOXN1 Italian founder mutation in Indian family: Implications in prenatal diagnosis","volume":"627","author":"Radha Rama Devi","year":"2017","journal-title":"Gene"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13085","article-title":"A novel PAX1 null homozygous mutation in autosomal recessive otofaciocervical syndrome associated with severe combined immunodeficiency","volume":"92","author":"Paganini","year":"2017","journal-title":"Clin Genet"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aax1036","article-title":"PAX1 is essential for development and function of the human thymus","volume":"5","author":"Yamazaki","year":"2020","journal-title":"Sci Immunol"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01908","article-title":"Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network","volume":"10","author":"Cirillo","year":"2019","journal-title":"Front Immunol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2265-1","article-title":"Whole-genome sequencing of a sporadic primary immunodeficiency cohort","volume":"583","author":"Thaventhiran","year":"2020","journal-title":"Nature"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.05.046","article-title":"Improving the diagnostic efficiency of primary immunodeficiencies with targeted next-generation sequencing","volume":"147","author":"Fusaro","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.08.027","article-title":"The genetic landscape of severe combined immunodeficiency in the United States and Canada in the current era (2010-2018)","volume":"143","author":"Dvorak","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B125","article-title":"Investigational cultured thymus tissue transplantation (RVT-802) following failed stem cell transplantationin athymic patients","author":"Tyler","year":"2019","journal-title":"CIS Abstract"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.9133","article-title":"Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States","volume":"312","author":"Kwan","year":"2014","journal-title":"JAMA"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02406","article-title":"First Universal Newborn Screening Program for Severe Combined Immunodeficiency in Europe. Two-Years\u2019 Experience in Catalonia (Spain)","volume":"10","author":"Argudo-Ramirez","year":"2019","journal-title":"Front Immunol"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1293","article-title":"Induction of T-cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro","volume":"105","author":"La Motte-Mohs","year":"2005","journal-title":"Blood"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.30916","article-title":"Biomaterial-based notch signaling for the differentiation of hematopoietic stem cells into T cells","volume":"79","author":"Taqvi","year":"2006","journal-title":"J BioMed Mater Res A"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4258","article-title":"Progenitor T-cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1","volume":"14","author":"Shukla","year":"2017","journal-title":"Nat Methods"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020001736","article-title":"Diagnostic assay to assist clinical decisions for unclassified severe combined immune deficiency","volume":"4","author":"Bifsha","year":"2020","journal-title":"Blood Adv"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.07.014","article-title":"Heterozygous FOXN1 Variants Cause Low TRECs and Severe T Cell Lymphopenia, Revealing a Crucial Role of FOXN1 in Supporting Early Thymopoiesis","volume":"105","author":"Bosticardo","year":"2019","journal-title":"Am J Hum Genet"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1172\/JCI127565","article-title":"FOXN1 compound heterozygous mutations cause selective thymic hypoplasia in humans","volume":"129","author":"Du","year":"2019","journal-title":"J Clin Invest"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.02.028","article-title":"Neonatal thymectomy in children-accelerating the immunologic clock","volume":"146","author":"Deya-Martinez","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"B135","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.1016\/j.jaci.2018.01.037","article-title":"Long-term clinical effects of early thymectomy: Associations with autoimmune diseases, cancer, infections, and atopic diseases","volume":"141","author":"Gudmundsdottir","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B136","doi-asserted-by":"publisher","first-page":"e13930","DOI":"10.1111\/petr.13930","article-title":"T cell phenotype in paediatric heart transplant recipients","author":"Mengrelis","year":"2020","journal-title":"Pediatr Transplant"},{"key":"B137","doi-asserted-by":"publisher","first-page":"e0230668","DOI":"10.1371\/journal.pone.0230668","article-title":"Histopathologic assessment of cultured human thymus","volume":"15","author":"Hale","year":"2020","journal-title":"PLoS One"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2545","article-title":"Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients","volume":"102","author":"Markert","year":"2003","journal-title":"Blood"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.6354","article-title":"Use of allograft biopsies to assess thymopoiesis after thymus transplantation","volume":"180","author":"Markert","year":"2008","journal-title":"J Immunol"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2008.02301.x","article-title":"Factors affecting success of thymus transplantation for complete DiGeorge anomaly","volume":"8","author":"Markert","year":"2008","journal-title":"Am J Transplant"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.11.009","article-title":"Long-term tolerance to allogeneic thymus transplants in complete DiGeorge anomaly","volume":"126","author":"Chinn","year":"2008","journal-title":"Clin Immunol"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15668","article-title":"Correction of both immunodeficiency and hypoparathyroidism by thymus transplantation in complete DiGeorge syndrome","volume":"20","author":"Kreins","year":"2020","journal-title":"Am J Transplant"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000120369.92378.54","article-title":"Tubular chimerism occurs regularly in renal allografts and is not correlated to outcome","volume":"15","author":"Mengel","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2004.029678","article-title":"Transbronchial biopsies provide longitudinal evidence for epithelial chimerism in children following sex mismatched lung transplantation","volume":"60","author":"Spencer","year":"2005","journal-title":"Thorax"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2011.04.004","article-title":"Thymic microenvironment reconstitution after postnatal human thymus transplantation","volume":"140","author":"Li","year":"2011","journal-title":"Clin Immunol"},{"key":"B146","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s12026-008-8083-4","article-title":"Characterization of cultured thymus tissue used for transplantation with emphasis on promiscuous expression of thyroid tissue-specific genes","volume":"44","author":"Li","year":"2009","journal-title":"Immunol Res"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747193","article-title":"Transplanted human thymus slices induce and support T-cell development in mice after cryopreservation","volume":"48","author":"Ross","year":"2018","journal-title":"Eur J Immunol"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00481","article-title":"Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency (SCID)","volume":"7","author":"Haddad","year":"2019","journal-title":"Front Pediatr"},{"key":"B149","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1016\/j.jaci.2019.05.042","article-title":"De novo generation of a functional human thymus from induced pluripotent stem cells","volume":"144","author":"Chhatta","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0000000000000695","article-title":"Replacing defective thymus function","volume":"20","author":"Kreins","year":"2020","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B151","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1089\/ten.teb.2016.0291","article-title":"Evaluating the Past, Present, and Future of Regenerative Medicine: A Global View","volume":"23","author":"Ronfard","year":"2017","journal-title":"Tissue Eng Part B Rev"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905955","article-title":"Limbal stem-cell therapy and long-term corneal regeneration","volume":"363","author":"Rama","year":"2010","journal-title":"N Engl J Med"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1038\/nature24487","article-title":"Regeneration of the entire human epidermis using transgenic stem cells","volume":"551","author":"Hirsch","year":"2017","journal-title":"Nature"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200012150-00009","article-title":"Long-term regeneration of human epidermis on third degree burns transplanted with autologous cultured epithelium grown on a fibrin matrix","volume":"70","author":"Ronfard","year":"2000","journal-title":"Transplantation"},{"key":"B155","doi-asserted-by":"publisher","first-page":"pdb prot4808","DOI":"10.1101\/pdb.prot4808","article-title":"Fetal thymus organ culture","volume":"2007","author":"Anderson","year":"2007","journal-title":"CSH Protoc"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1089\/152581603322448277","article-title":"T cell generation including positive and negative selection ex vivo in a three-dimensional matrix","volume":"12","author":"Marshall","year":"2003","journal-title":"J Hematother Stem Cell Res"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1038\/77288","article-title":"Efficient generation of human T cells from a tissue-engineered thymic organoid","volume":"18","author":"Poznansky","year":"2000","journal-title":"Nat Biotechnol"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.02.045","article-title":"p63 Is essential for the proliferative potential of stem cells in stratified epithelia","volume":"129","author":"Senoo","year":"2007","journal-title":"Cell"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1038\/nature09269","article-title":"Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells","volume":"466","author":"Bonfanti","year":"2010","journal-title":"Nature"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.07.029","article-title":"Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus","volume":"8","author":"Wong","year":"2014","journal-title":"Cell Rep"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1002\/sctm.18-0218","article-title":"Gene Modification and Three-Dimensional Scaffolds as Novel Tools to Allow the Use of Postnatal Thymic Epithelial Cells for Thymus Regeneration Approaches","volume":"8","author":"Bortolomai","year":"2019","journal-title":"Stem Cells Transl Med"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.77","article-title":"Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts","volume":"23","author":"Fan","year":"2015","journal-title":"Mol Ther"},{"key":"B163","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biomaterials.2016.11.054","article-title":"Native thymic extracellular matrix improves in vivo thymic organoid T cell output, and drives in vitro thymic epithelial cell differentiation","volume":"118","author":"Hun","year":"2017","journal-title":"Biomaterials"},{"key":"B164","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/7651_2016_9","article-title":"Construction of Thymus Organoids from Decellularized Thymus Scaffolds","volume":"1576","author":"Tajima","year":"2019","journal-title":"Methods Mol Biol"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3023","article-title":"An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts","volume":"16","author":"Bredenkamp","year":"2014","journal-title":"Nat Cell Biol"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.04.004","article-title":"Generation of functional thymic epithelium from human embryonic stem cells that supports host T cell development","volume":"13","author":"Parent","year":"2013","journal-title":"Cell Stem Cell"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2013.06.014","article-title":"Directed differentiation of human embryonic stem cells into thymic epithelial progenitor-like cells reconstitutes the thymic microenvironment in vivo","volume":"13","author":"Sun","year":"2013","journal-title":"Cell Stem Cell"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.655354\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T10:02:34Z","timestamp":1698055354000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.655354\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,18]]},"references-count":167,"alternative-id":["10.3389\/fimmu.2021.655354"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.655354","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,18]]},"article-number":"655354"}}