{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T18:52:17Z","timestamp":1781722337939,"version":"3.54.5"},"reference-count":83,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This review summarizes key topics discussed in the session \u201cBiology within the Thymus\u201d at the 54th Annual Meeting of the Japanese Society for Immunology, which highlighted recent advances in our understanding of T-cell development and fate determination. In particular, the session focused on transcriptional regulation of T-lineage commitment and the mechanisms by which T-cell receptor (TCR) signaling governs thymocyte differentiation. Early T-lineage commitment is established through the integration of thymic microenvironmental cues and intrinsic transcription factors, including Bcl11b, PU.1, and Runx family proteins. Among these, Runx transcription factors play essential roles throughout thymocyte development, not primarily through changes in expression but through dynamic regulation of their molecular interactions and genomic occupancy. Following commitment, \u03b1\u03b2TCR-expressing CD4+CD8+ double-positive (DP) thymocytes undergo MHC-dependent selection and differentiate into CD4+ helper or CD8+ cytotoxic T cells. Although the core components of proximal TCR signaling are largely shared, accumulating observations suggest that qualitative and quantitative differences in signaling\u2014shaped by signal strength, duration, and subcellular context\u2014may contribute to lineage specification. In this regard, recent studies discussed in this session highlighted the role of co-receptor\u2013free Lck as an active signaling pool capable of initiating TCR signaling independently of CD4 or CD8 association, thereby adding an additional layer of complexity to MHC-dependent thymic selection. In addition, post-translational modification of Runx proteins, particularly within the conserved WRPY motif, has emerged as a molecular link between proximal TCR signaling mediated by kinases such as Lck and lineage-specific transcriptional repression. Together with advances in thymic culture systems, genome editing, and proteomic approaches, these findings underscore the tight coupling between proximal TCR signaling\u2014including both co-receptor\u2013dependent and co-receptor\u2013independent Lck activity\u2014and transcriptional regulation, and highlight Runx transcription factors as key integrators that translate MHC-specific TCR signals into transcriptional programs determining thymocyte fate.<\/jats:p>","DOI":"10.1093\/intimm\/dxag030","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:48:15Z","timestamp":1780487295000},"source":"Crossref","is-referenced-by-count":0,"title":["Signaling and transcriptional control of thymocyte differentiation"],"prefix":"10.1093","author":[{"given":"Ichiro","family":"Taniuchi","sequence":"first","affiliation":[{"name":"Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences (IMS) , 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"2026061714094555900_dxag030-B1","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.it.2006.08.004","article-title":"Thymus-homing precursors and the thymic microenvironment","volume":"27","author":"Boehm","year":"2006","journal-title":"Trends Immunol"},{"key":"2026061714094555900_dxag030-B2","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/82_2013_324","article-title":"Trafficking to the thymus","volume":"373","author":"Zhang","year":"2014","journal-title":"Curr Top Microbiol Immunol"},{"key":"2026061714094555900_dxag030-B3","doi-asserted-by":"publisher","first-page":"2531","DOI":"10.1182\/blood-2006-05-024190","article-title":"Coordination between CCR7- and CCR9-mediated chemokine signals in prevascular fetal thymus colonization","volume":"108","author":"Liu","year":"2006","journal-title":"Blood"},{"key":"2026061714094555900_dxag030-B4","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.4049\/jimmunol.168.6.2811","article-title":"A role for CCR9 in T lymphocyte development and migration","volume":"168","author":"Uehara","year":"2002","journal-title":"J Immunol"},{"key":"2026061714094555900_dxag030-B5","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.1084\/jem.20080134","article-title":"Delta-like 4 is indispensable in thymic environment specific for T cell development","volume":"205","author":"Hozumi","year":"2008","journal-title":"J Exp Med"},{"key":"2026061714094555900_dxag030-B6","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1146\/annurev.immunol.17.1.523","article-title":"The regulation of CD4 and CD8 coreceptor gene expression during T cell development","volume":"17","author":"Ellmeier","year":"1999","journal-title":"Annu Rev Immunol"},{"key":"2026061714094555900_dxag030-B7","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1126\/science.1188989","article-title":"An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b","volume":"329","author":"Li","year":"2010","journal-title":"Science"},{"key":"2026061714094555900_dxag030-B8","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1126\/science.1188995","article-title":"An essential developmental checkpoint for production of the T cell lineage","volume":"329","author":"Ikawa","year":"2010","journal-title":"Science"},{"key":"2026061714094555900_dxag030-B9","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1126\/science.1188063","article-title":"Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion","volume":"329","author":"Li","year":"2010","journal-title":"Science"},{"key":"2026061714094555900_dxag030-B10","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1038\/ni.3514","article-title":"Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment","volume":"17","author":"Kueh","year":"2016","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B11","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/ni925","article-title":"Bcl11a is essential for normal lymphoid development","volume":"4","author":"Liu","year":"2003","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B12","doi-asserted-by":"publisher","first-page":"2165","DOI":"10.1056\/NEJMoa1509164","article-title":"Multisystem anomalies in severe combined immunodeficiency with mutant BCL11B","volume":"375","author":"Punwani","year":"2016","journal-title":"N Engl J Med"},{"key":"2026061714094555900_dxag030-B13","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1093\/brain\/awy173","article-title":"BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells","volume":"141","author":"Lessel","year":"2018","journal-title":"Brain"},{"key":"2026061714094555900_dxag030-B14","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1038\/s41590-024-01997-5","article-title":"A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development","volume":"25","author":"Okuyama","year":"2024","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B15","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1038\/s41590-021-00951-z","article-title":"A variant in human AIOLOS impairs adaptive immunity by interfering with IKAROS","volume":"22","author":"Yamashita","year":"2021","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B16","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/0092-8674(94)90407-3","article-title":"The Ikaros gene is required for the development of all lymphoid lineages","volume":"79","author":"Georgopoulos","year":"1994","journal-title":"Cell"},{"key":"2026061714094555900_dxag030-B17","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/S1074-7613(00)80637-8","article-title":"Aiolos regulates B cell activation and maturation to effector state","volume":"9","author":"Wang","year":"1998","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B18","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/44076","article-title":"Commitment to the B-lymphoid lineage depends on the transcription factor Pax5","volume":"401","author":"Nutt","year":"1999","journal-title":"Nature"},{"key":"2026061714094555900_dxag030-B19","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1101\/gad.6.9.1589","article-title":"Pax-5 encodes the transcription factor BSAP and is expressed in B lymphocytes, the developing CNS, and adult testis","volume":"6","author":"Adams","year":"1992","journal-title":"Genes Dev"},{"key":"2026061714094555900_dxag030-B20","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1101\/gad.11.4.476","article-title":"Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus","volume":"11","author":"Nutt","year":"1997","journal-title":"Genes Dev"},{"key":"2026061714094555900_dxag030-B21","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1084\/jem.20021765","article-title":"In vitro evidence that cytokine receptor signals are required for differentiation of double positive thymocytes into functionally mature CD8+ T cells","volume":"197","author":"Yu","year":"2003","journal-title":"J Exp Med"},{"key":"2026061714094555900_dxag030-B22","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/s41577-020-00426-6","article-title":"How transcription factors drive choice of the T cell fate","volume":"21","author":"Hosokawa","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"2026061714094555900_dxag030-B23","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1101\/gad.297002.117","article-title":"The making of a lymphocyte: the choice among disparate cell fates and the IKAROS enigma","volume":"31","author":"Georgopoulos","year":"2017","journal-title":"Genes Dev"},{"key":"2026061714094555900_dxag030-B24","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1182\/blood-2007-10-120261","article-title":"Core binding factors are necessary for natural killer cell development and cooperate with Notch signaling during T-cell specification","volume":"112","author":"Guo","year":"2008","journal-title":"Blood"},{"key":"2026061714094555900_dxag030-B25","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.cell.2018.12.036","article-title":"The cis-regulatory atlas of the mouse immune system","volume":"176","author":"Yoshida","year":"2019","journal-title":"Cell"},{"key":"2026061714094555900_dxag030-B26","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.immuni.2018.04.024","article-title":"Transcription factor PU.1 represses and activates gene expression in early T cells by redirecting partner transcription factor binding","volume":"48","author":"Hosokawa","year":"2018","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B27","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1038\/s41590-018-0238-4","article-title":"Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16","volume":"19","author":"Hosokawa","year":"2018","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B28","doi-asserted-by":"publisher","first-page":"749","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":"2026061714094555900_dxag030-B29","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.4049\/jimmunol.174.5.2507","article-title":"Polycomb group gene mel-18 regulates early T progenitor expansion by maintaining the expression of Hes-1, a target of the Notch pathway","volume":"174","author":"Miyazaki","year":"2005","journal-title":"J Immunol"},{"key":"2026061714094555900_dxag030-B30","doi-asserted-by":"publisher","first-page":"eabm1920","DOI":"10.1126\/sciimmunol.abm1920","article-title":"Single-cell deletion analyses show control of pro-T cell developmental speed and pathways by Tcf7, Spi1, Gata3, Bcl11a, Erg, and Bcl11b","volume":"7","author":"Zhou","year":"2022","journal-title":"Sci Immunol"},{"key":"2026061714094555900_dxag030-B31","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/S1074-7613(04)00049-4","article-title":"Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent","volume":"20","author":"Ikawa","year":"2004","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B32","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/ni1555","article-title":"Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5","volume":"9","author":"Pongubala","year":"2008","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B33","doi-asserted-by":"publisher","first-page":"e20250911","DOI":"10.1084\/jem.20250911","article-title":"Notch interaction with RUNX factors regulates initiation of the T-lineage program","volume":"223","author":"Kama","year":"2026","journal-title":"J Exp Med"},{"key":"2026061714094555900_dxag030-B34","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41586-019-1244-x","article-title":"Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation","volume":"571","author":"Wilkinson","year":"2019","journal-title":"Nature"},{"key":"2026061714094555900_dxag030-B35","doi-asserted-by":"publisher","first-page":"eadw7765","DOI":"10.1126\/sciimmunol.adw7765","article-title":"T cell development from expanded hematopoietic progenitors reveals initiation control by Lmo2 and Flt3L priming","volume":"11","author":"Shin","year":"2026","journal-title":"Sci Immunol"},{"key":"2026061714094555900_dxag030-B36","doi-asserted-by":"publisher","first-page":"108320","DOI":"10.1016\/j.celrep.2020.108320","article-title":"In vitro recapitulation of murine thymopoiesis from single hematopoietic stem cells","volume":"33","author":"Montel-Hagen","year":"2020","journal-title":"Cell Rep"},{"key":"2026061714094555900_dxag030-B37","doi-asserted-by":"publisher","first-page":"e403","DOI":"10.1002\/cpz1.403","article-title":"Generation of artificial thymic organoids from human and murine hematopoietic stem and progenitor cells","volume":"2","author":"Montel-Hagen","year":"2022","journal-title":"Curr Protoc"},{"key":"2026061714094555900_dxag030-B38","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/s41577-023-00911-8","article-title":"A guide to thymic selection of T cells","volume":"24","author":"Ashby","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"2026061714094555900_dxag030-B39","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/nri2416","article-title":"Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice","volume":"8","author":"Singer","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"2026061714094555900_dxag030-B40","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1146\/annurev-immunol-042617-053411","article-title":"CD4 helper and CD8 cytotoxic T cell differentiation","volume":"36","author":"Taniuchi","year":"2018","journal-title":"Annu Rev Immunol"},{"key":"2026061714094555900_dxag030-B41","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1084\/jem.170.5.1671","article-title":"Engagement of CD4 and CD8 expressed on immature thymocytes induces activation of intracellular tyrosine phosphorylation pathways","volume":"170","author":"Veillette","year":"1989","journal-title":"J Exp Med"},{"key":"2026061714094555900_dxag030-B42","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1084\/jem.178.5.1701","article-title":"Regulation of T cell receptor expression in immature CD4+CD8+ thymocytes by p56lck tyrosine kinase: basis for differential signaling by CD4 and CD8 in immature thymocytes expressing both coreceptor molecules","volume":"178","author":"Wiest","year":"1993","journal-title":"J Exp Med"},{"key":"2026061714094555900_dxag030-B43","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1084\/jem.184.3.931","article-title":"Requirement for p56lck tyrosine kinase activation in T cell receptor-mediated thymic selection","volume":"184","author":"Hashimoto","year":"1996","journal-title":"J Exp Med"},{"key":"2026061714094555900_dxag030-B44","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1073\/pnas.90.2.442","article-title":"The conserved lysine of the catalytic domain of protein kinases is actively involved in the phosphotransfer reaction and not required for anchoring ATP","volume":"90","author":"Carrera","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061714094555900_dxag030-B45","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1128\/mcb.8.2.540-550.1988","article-title":"Neoplastic transformation induced by an activated lymphocyte-specific protein tyrosine kinase (pp56lck)","volume":"8","author":"Marth","year":"1988","journal-title":"Mol Cell Biol"},{"key":"2026061714094555900_dxag030-B46","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/S1074-7613(00)80184-3","article-title":"Lck activity controls CD4\/CD8 T cell lineage commitment","volume":"12","author":"Hernandez-Hoyos","year":"2000","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B47","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/S1074-7613(01)00128-5","article-title":"Strength of signaling by CD4 and CD8 coreceptor tails determines the number but not the lineage direction of positively selected thymocytes","volume":"14","author":"Bosselut","year":"2001","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B48","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/s41467-020-20306-w","article-title":"The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus","volume":"12","author":"Karimi","year":"2021","journal-title":"Nat Commun"},{"key":"2026061714094555900_dxag030-B49","doi-asserted-by":"publisher","first-page":"E5891","DOI":"10.1073\/pnas.1701990114","article-title":"Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling","volume":"114","author":"Li","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061714094555900_dxag030-B50","doi-asserted-by":"publisher","first-page":"15809","DOI":"10.1073\/pnas.1913334117","article-title":"Lck bound to coreceptor is less active than free Lck","volume":"117","author":"Wei","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061714094555900_dxag030-B51","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1016\/0092-8674(90)90090-2","article-title":"Interaction of the unique N-terminal region of tyrosine kinase p56lck with cytoplasmic domains of CD4 and CD8 is mediated by cysteine motifs","volume":"60","author":"Turner","year":"1990","journal-title":"Cell"},{"key":"2026061714094555900_dxag030-B52","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1126\/science.1085643","article-title":"A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8","volume":"301","author":"Kim","year":"2003","journal-title":"Science"},{"key":"2026061714094555900_dxag030-B53","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/s41590-022-01366-0","article-title":"Unique roles of co-receptor-bound LCK in helper and cytotoxic T cells","volume":"24","author":"Horkova","year":"2023","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B54","doi-asserted-by":"publisher","first-page":"eadp5016","DOI":"10.1126\/sciimmunol.adp5016","article-title":"LCK-co-receptor association ensures T cell lineage fidelity and maximizes epitope-specific TCR diversity","volume":"10","author":"Zhang","year":"2025","journal-title":"Sci Immunol"},{"key":"2026061714094555900_dxag030-B55","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1016\/j.cell.2013.08.009","article-title":"Lck availability during thymic selection determines the recognition specificity of the T cell repertoire","volume":"154","author":"Van Laethem","year":"2013","journal-title":"Cell"},{"key":"2026061714094555900_dxag030-B56","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/1074-7613(95)90149-3","article-title":"Asymmetric signaling requirements for thymocyte commitment to the CD4+ versus CD8+ T cell lineages: a new perspective on thymic commitment and selection","volume":"2","author":"Suzuki","year":"1995","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B57","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/S1074-7613(00)00008-X","article-title":"Coreceptor reversal in the thymus: signaled CD4+8+ thymocytes initially terminate CD8 transcription even when differentiating into CD8+ T cells","volume":"13","author":"Brugnera","year":"2000","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B58","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.immuni.2005.05.011","article-title":"Modulation of coreceptor transcription during positive selection dictates lineage fate independently of TCR\/coreceptor specificity","volume":"23","author":"Sarafova","year":"2005","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B59","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/emboj.2011.388","article-title":"Coreceptor gene imprinting governs thymocyte lineage fate","volume":"31","author":"Adoro","year":"2012","journal-title":"Embo J"},{"key":"2026061714094555900_dxag030-B60","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.immuni.2009.07.006","article-title":"Upregulation of CD4 expression during MHC class II-specific positive selection is essential for error-free lineage choice","volume":"31","author":"Sarafova","year":"2009","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B61","doi-asserted-by":"publisher","first-page":"e202000642","DOI":"10.26508\/lsa.202000642","article-title":"Constitutive CD8 expression drives innate CD8(+) T-cell differentiation via induction of iNKT2 cells","volume":"3","author":"Kojo","year":"2020","journal-title":"Life Sci Alliance"},{"key":"2026061714094555900_dxag030-B62","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41590-022-01187-1","article-title":"Reversal of the T cell immune system reveals the molecular basis for T cell lineage fate determination in the thymus","volume":"23","author":"Shinzawa","year":"2022","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B63","doi-asserted-by":"publisher","first-page":"4537","DOI":"10.1007\/s00018-013-1393-2","article-title":"Transcriptional control of CD4 and CD8 coreceptor expression during T cell development","volume":"70","author":"Ellmeier","year":"2013","journal-title":"Cell Mol Life Sci"},{"key":"2026061714094555900_dxag030-B64","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/S1074-7613(00)80375-1","article-title":"An enhancer that directs lineage-specific expression of CD8 in positively selected thymocytes and mature T cells","volume":"7","author":"Ellmeier","year":"1997","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B65","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/S1074-7613(00)80632-9","article-title":"Multiple developmental stage-specific enhancers regulate CD8 expression in developing thymocytes and in thymus-independent T cells","volume":"9","author":"Ellmeier","year":"1998","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B66","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/0092-8674(94)90140-6","article-title":"A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development","volume":"77","author":"Sawada","year":"1994","journal-title":"Cell"},{"key":"2026061714094555900_dxag030-B67","doi-asserted-by":"publisher","first-page":"3570","DOI":"10.1002\/j.1460-2075.1994.tb06664.x","article-title":"A transcriptional silencer controls the developmental expression of the CD4 gene","volume":"13","author":"Siu","year":"1994","journal-title":"Embo J"},{"key":"2026061714094555900_dxag030-B68","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/ng750","article-title":"Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage","volume":"29","author":"Zou","year":"2001","journal-title":"Nat Genet"},{"key":"2026061714094555900_dxag030-B69","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1038\/ni733","article-title":"Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment","volume":"2","author":"Leung","year":"2001","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B70","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/s41467-017-00768-1","article-title":"Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes","volume":"8","author":"Kojo","year":"2017","journal-title":"Nat Commun"},{"key":"2026061714094555900_dxag030-B71","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1016\/j.celrep.2017.04.038","article-title":"Essential roles of SATB1 in specifying T lymphocyte subsets","volume":"19","author":"Kakugawa","year":"2017","journal-title":"Cell Rep"},{"key":"2026061714094555900_dxag030-B72","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/S0092-8674(02)01111-X","article-title":"Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development","volume":"111","author":"Taniuchi","year":"2002","journal-title":"Cell"},{"key":"2026061714094555900_dxag030-B73","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1126\/science.1151844","article-title":"Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development","volume":"319","author":"Setoguchi","year":"2008","journal-title":"Science"},{"key":"2026061714094555900_dxag030-B74","doi-asserted-by":"publisher","first-page":"11590","DOI":"10.1073\/pnas.95.20.11590","article-title":"Transcriptional repression by AML1 and LEF-1 is mediated by the TLE\/Groucho corepressors","volume":"95","author":"Levanon","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061714094555900_dxag030-B75","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.molcel.2006.04.024","article-title":"Molecular recognition of transcriptional repressor motifs by the WD domain of the Groucho\/TLE corepressor","volume":"22","author":"Jennings","year":"2006","journal-title":"Mol Cell"},{"key":"2026061714094555900_dxag030-B76","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/nature03338","article-title":"The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment","volume":"433","author":"He","year":"2005","journal-title":"Nature"},{"key":"2026061714094555900_dxag030-B77","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/ni1183","article-title":"The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection","volume":"6","author":"Sun","year":"2005","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B78","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.immuni.2008.02.006","article-title":"CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus","volume":"28","author":"He","year":"2008","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B79","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.immuni.2008.02.011","article-title":"Thymus lineage commitment: a single switch","volume":"28","author":"Hedrick","year":"2008","journal-title":"Immunity"},{"key":"2026061714094555900_dxag030-B80","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/s41590-026-02441-6","article-title":"Phosphorylation of Runx protein controls helper CD4(+) T cell versus cytotoxic CD8(+) T cell lineage choice","volume":"27","author":"Ogawa","year":"2026","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B81","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/S0092-8674(00)80986-1","article-title":"AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis","volume":"84","author":"Okuda","year":"1996","journal-title":"Cell"},{"key":"2026061714094555900_dxag030-B82","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1038\/s41590-019-0489-8","article-title":"Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics","volume":"20","author":"Voisinne","year":"2019","journal-title":"Nat Immunol"},{"key":"2026061714094555900_dxag030-B83","doi-asserted-by":"publisher","first-page":"e20211295","DOI":"10.1084\/jem.20211295","article-title":"Systems-level conservation of the proximal TCR signaling network of mice and humans","volume":"219","author":"Nicolas","year":"2022","journal-title":"J Exp Med"}],"container-title":["International Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/intimm\/advance-article-pdf\/doi\/10.1093\/intimm\/dxag030\/68466312\/dxag030.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/advance-article-pdf\/doi\/10.1093\/intimm\/dxag030\/68466312\/dxag030.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T18:09:56Z","timestamp":1781719796000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/intimm\/advance-article\/doi\/10.1093\/intimm\/dxag030\/8701200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":83,"URL":"https:\/\/doi.org\/10.1093\/intimm\/dxag030","relation":{},"ISSN":["1460-2377"],"issn-type":[{"value":"1460-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]},"article-number":"dxag030"}}