{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:23:14Z","timestamp":1792002194605,"version":"4.4.0"},"reference-count":113,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":379,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Immunity"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1016\/j.immuni.2020.10.024","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T10:45:30Z","timestamp":1606301130000},"page":"1182-1201.e8","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":84,"title":["An Integrated Epigenomic and Transcriptomic Map of Mouse and Human \u03b1\u03b2 T Cell Development"],"prefix":"10.1016","volume":"53","author":[{"given":"Laura B.","family":"Chopp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishaka","family":"Gopalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ciucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Ruchinskas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Rae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Lagarde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayi","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marita","family":"Bosticardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Livak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Hannenhalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9my","family":"Bosselut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.immuni.2020.10.024_bib1","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib2","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.immuni.2020.10.024_bib3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1084\/jem.20071944","article-title":"Development of all CD4\u00a0T lineages requires nuclear factor TOX","volume":"205","author":"Aliahmad","year":"2008","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib4","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"10.1016\/j.immuni.2020.10.024_bib5","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/ni.2918","article-title":"Quantitative and temporal requirements revealed for Zap70 catalytic activity during T\u00a0cell development","volume":"15","author":"Au-Yeung","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib6","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1084\/jem.188.12.2301","article-title":"CD5 expression is developmentally regulated by T\u00a0cell receptor (TCR) signals and TCR avidity","volume":"188","author":"Azzam","year":"1998","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib7","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J.\u00a0R. Stat. Soc. B"},{"key":"10.1016\/j.immuni.2020.10.024_bib8","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.immuni.2020.10.024_bib9","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/415922a","article-title":"BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes","volume":"415","author":"Bouillet","year":"2002","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2020.10.024_bib10","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/nmeth.2688","article-title":"Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position","volume":"10","author":"Buenrostro","year":"2013","journal-title":"Nat. Methods"},{"key":"10.1016\/j.immuni.2020.10.024_bib11","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature14590","article-title":"Single-cell chromatin accessibility reveals principles of regulatory variation","volume":"523","author":"Buenrostro","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2020.10.024_bib12","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.immuni.2020.10.024_bib13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.molcel.2019.04.030","article-title":"Topoisomerase II-induced chromosome breakage and translocation is determined by chromosome architecture and transcriptional activity","volume":"75","author":"Canela","year":"2019","journal-title":"Mol. Cell"},{"key":"10.1016\/j.immuni.2020.10.024_bib14","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","article-title":"The single-cell transcriptional landscape of mammalian organogenesis","volume":"566","author":"Cao","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2020.10.024_bib15","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/ni.1887","article-title":"Decision checkpoints in the thymus","volume":"11","author":"Carpenter","year":"2010","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib16","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.immuni.2012.06.019","article-title":"The transcription factors Thpok and LRF are necessary and partly redundant for T helper cell differentiation","volume":"37","author":"Carpenter","year":"2012","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib17","doi-asserted-by":"crossref","first-page":"15081","DOI":"10.1038\/ncomms15081","article-title":"Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer","volume":"8","author":"Chung","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.immuni.2020.10.024_bib18","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.immuni.2018.12.019","article-title":"The emergence and functional fitness of memory CD4+ T\u00a0cells require the transcription factor Thpok","volume":"50","author":"Ciucci","year":"2019","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib19","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nri2489","article-title":"RUNX proteins in transcription factor networks that regulate T-cell lineage choice","volume":"9","author":"Collins","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/ni1038","article-title":"Ternary complex factor SAP-1 is required for Erk-mediated thymocyte positive selection","volume":"5","author":"Costello","year":"2004","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib21","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1084\/jem.20122070","article-title":"The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development","volume":"210","author":"Cowan","year":"2013","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib22","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1084\/jem.20121458","article-title":"Helios marks strongly autoreactive CD4+ T\u00a0cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-\u03baB","volume":"210","author":"Daley","year":"2013","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib23","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/nature05269","article-title":"Thymic selection threshold defined by compartmentalization of Ras\/MAPK signalling","volume":"444","author":"Daniels","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2020.10.024_bib24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"10.1016\/j.immuni.2020.10.024_bib114","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s11248-005-7220-2","article-title":"A generic tool for biotinylation of tagged proteins in transgenic mice","volume":"14","author":"Driegen","year":"2005","journal-title":"Transgenic Res."},{"key":"10.1016\/j.immuni.2020.10.024_bib25","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/ni.1652","article-title":"ThPOK acts late in specification of the helper T\u00a0cell lineage and suppresses Runx-mediated commitment to the cytotoxic T\u00a0cell lineage","volume":"9","author":"Egawa","year":"2008","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib26","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1084\/jem.20070133","article-title":"The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T\u00a0cells","volume":"204","author":"Egawa","year":"2007","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib27","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1126\/science.1910207","article-title":"Depletion of CD4+ T\u00a0cells in major histocompatibility complex class II-deficient mice","volume":"253","author":"Grusby","year":"1991","journal-title":"Science"},{"key":"10.1016\/j.immuni.2020.10.024_bib28","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nbt.4091","article-title":"Batch effects in single-cell RNA-sequencing data are corrected by matching mutual nearest neighbors","volume":"36","author":"Haghverdi","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.immuni.2020.10.024_bib29","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib30","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib31","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol. Cell"},{"key":"10.1016\/j.immuni.2020.10.024_bib32","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1084\/jem.20190993","article-title":"IL-2 production by self-reactive CD4 thymocytes scales regulatory T\u00a0cell generation in the thymus","volume":"216","author":"Hemmers","year":"2019","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib33","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1074-7613(03)00176-6","article-title":"GATA-3 expression is controlled by TCR signals and regulates CD4\/CD8 differentiation","volume":"19","author":"Hern\u00e1ndez-Hoyos","year":"2003","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib34","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/ni.2938","article-title":"The self-obsession of T\u00a0cells: how TCR signaling thresholds affect fate \u2018decisions\u2019 and effector function","volume":"15","author":"Hogquist","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib35","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1038\/s41467-019-10525-1","article-title":"Identification of a genomic enhancer that enforces proper apoptosis induction in thymic negative selection","volume":"10","author":"Hojo","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.immuni.2020.10.024_bib36","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.immuni.2012.02.010","article-title":"E protein transcription factors are required for the development of CD4(+) lineage T\u00a0cells","volume":"36","author":"Jones-Mason","year":"2012","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib37","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib38","article-title":"CellOracle: dissecting cell identity via network inference and in\u00a0silico gene perturbation","author":"Kamimoto","year":"2020","journal-title":"bioRxiv"},{"key":"10.1016\/j.immuni.2020.10.024_bib39","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nri2507","article-title":"E and ID proteins branch out","volume":"9","author":"Kee","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib40","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"10.1016\/j.immuni.2020.10.024_bib41","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib42","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib43","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/ni.1641","article-title":"The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T\u00a0cell effector functions","volume":"9","author":"Kovalovsky","year":"2008","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib44","doi-asserted-by":"crossref","first-page":"3999","DOI":"10.4049\/jimmunol.172.7.3999","article-title":"CCR7 directs the migration of thymocytes into the thymic medulla","volume":"172","author":"Kwan","year":"2004","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib45","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.immuni.2020.10.024_bib46","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib47","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.immuni.2020.05.010","article-title":"Single-cell RNA-seq mapping of human thymopoiesis reveals lineage specification trajectories and a commitment spectrum in T\u00a0cell development","volume":"52","author":"Le","year":"2020","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib48","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.4049\/jimmunol.0901304","article-title":"Rare development of Foxp3+ thymocytes in the CD4+CD8+ subset","volume":"183","author":"Lee","year":"2009","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib49","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S1074-7613(01)00227-8","article-title":"A critical role for Dnmt1 and DNA methylation in T\u00a0cell development, function, and survival","volume":"15","author":"Lee","year":"2001","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib50","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cell.2015.05.047","article-title":"Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis","volume":"162","author":"Levine","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2020.10.024_bib51","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nri.2016.26","article-title":"T cell receptor signalling in the control of regulatory T\u00a0cell differentiation and function","volume":"16","author":"Li","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib52","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.immuni.2020.10.024_bib53","doi-asserted-by":"crossref","first-page":"4465","DOI":"10.4049\/jimmunol.175.7.4465","article-title":"Analyzing expression of perforin, Runx3, and Thpok genes during positive selection reveals activation of CD8-differentiation programs by MHC II-signaled thymocytes","volume":"175","author":"Liu","year":"2005","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib54","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold\u00a0change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"10.1016\/j.immuni.2020.10.024_bib55","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/ni.2917","article-title":"The transcription factor ThPOK suppresses Runx3 and imposes CD4(+) lineage fate by inducing the SOCS suppressors of cytokine signaling","volume":"15","author":"Luckey","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib56","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/ni.2849","article-title":"Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T\u00a0cells","volume":"15","author":"Mahmud","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib57","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev.immunol.21.120601.141029","article-title":"Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more","volume":"21","author":"Marsden","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib58","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s41577-018-0013-7","article-title":"Diverse developmental pathways of intestinal intraepithelial lymphocytes","volume":"18","author":"McDonald","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib59","doi-asserted-by":"crossref","first-page":"4838","DOI":"10.4049\/jimmunol.0902208","article-title":"Cutting edge: Extracellular signal-related kinase is not required for negative selection of developing T\u00a0cells","volume":"183","author":"McGargill","year":"2009","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib60","doi-asserted-by":"crossref","first-page":"ra92","DOI":"10.1126\/scisignal.2004400","article-title":"Distinct temporal patterns of T\u00a0cell receptor signaling during positive versus negative selection in\u00a0situ","volume":"6","author":"Melichar","year":"2013","journal-title":"Sci. Signal."},{"key":"10.1016\/j.immuni.2020.10.024_bib61","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/ni.2590","article-title":"The transcriptional landscape of \u03b1\u03b2 T\u00a0cell differentiation","volume":"14","author":"Mingueneau","year":"2013","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib62","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1084\/jem.20110308","article-title":"T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse","volume":"208","author":"Moran","year":"2011","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib63","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/s00335-015-9583-x","article-title":"Creating reference gene annotation for the mouse C57BL6\/J genome assembly","volume":"26","author":"Mudge","year":"2015","journal-title":"Mamm. Genome"},{"key":"10.1016\/j.immuni.2020.10.024_bib64","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ni.1650","article-title":"Cascading suppression of transcriptional silencers by ThPOK seals helper T\u00a0cell fate","volume":"9","author":"Muroi","year":"2008","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib65","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.immuni.2013.03.002","article-title":"Development and maintenance of regulatory T\u00a0cells","volume":"38","author":"Ohkura","year":"2013","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib66","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S1074-7613(03)00328-5","article-title":"Critical roles for transcription factor GATA-3 in thymocyte development","volume":"19","author":"Pai","year":"2003","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib67","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nri1085","article-title":"Negative selection\u2014clearing out the bad apples from the T-cell repertoire","volume":"3","author":"Palmer","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib68","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nri.2017.76","article-title":"Single-cell RNA sequencing to explore immune cell heterogeneity","volume":"18","author":"Papalexi","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib69","doi-asserted-by":"crossref","first-page":"eaay3224","DOI":"10.1126\/science.aay3224","article-title":"A cell atlas of human thymic development defines T\u00a0cell repertoire formation","volume":"367","author":"Park","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.immuni.2020.10.024_bib70","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.molcel.2018.06.044","article-title":"Cicero predicts cis-regulatory DNA interactions from single-cell chromatin accessibility data","volume":"71","author":"Pliner","year":"2018","journal-title":"Mol. Cell"},{"key":"10.1016\/j.immuni.2020.10.024_bib71","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nmeth.4150","article-title":"Single-cell mRNA quantification and differential analysis with Census","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.immuni.2020.10.024_bib72","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.immuni.2020.10.024_bib73","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1084\/jem.20142110","article-title":"Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T\u00a0cells using MR1 tetramers","volume":"212","author":"Rahimpour","year":"2015","journal-title":"J.\u00a0Exp. Med."},{"issue":"W1","key":"10.1016\/j.immuni.2020.10.024_bib74","doi-asserted-by":"crossref","first-page":"W160","DOI":"10.1093\/nar\/gkw257","article-title":"deepTools2: a next generation web server for deep-sequencing data analysis","volume":"44","author":"Ram\u00edrez","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.immuni.2020.10.024_bib75","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nature10730","article-title":"Differential oestrogen receptor binding is associated with clinical outcome in breast cancer","volume":"481","author":"Ross-Innes","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2020.10.024_bib76","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1101\/gad.327163.119","article-title":"Programming for T-lymphocyte fates: modularity and mechanisms","volume":"33","author":"Rothenberg","year":"2019","journal-title":"Genes Dev."},{"key":"10.1016\/j.immuni.2020.10.024_bib77","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.coi.2019.04.010","article-title":"Development, ontogeny, and maintenance of TCR\u03b1\u03b2+ CD8\u03b1\u03b1 IEL","volume":"58","author":"Ruscher","year":"2019","journal-title":"Curr. Opin. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib78","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/ni.1860","article-title":"The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes","volume":"11","author":"Sakaguchi","year":"2010","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib79","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.immuni.2008.07.011","article-title":"The transcription factor PLZF directs the effector program of the NKT cell lineage","volume":"29","author":"Savage","year":"2008","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib80","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nmeth.4401","article-title":"chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data","volume":"14","author":"Schep","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.immuni.2020.10.024_bib81","doi-asserted-by":"crossref","first-page":"5203","DOI":"10.4049\/jimmunol.175.8.5203","article-title":"Human high mobility group box transcription factor 1 affects thymocyte development and transgene variegation","volume":"175","author":"Sekkali","year":"2005","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib82","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1126\/science.aae0491","article-title":"The epigenetic landscape of T\u00a0cell exhaustion","volume":"354","author":"Sen","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.immuni.2020.10.024_bib83","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1126\/science.1151844","article-title":"Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T\u00a0cell development","volume":"319","author":"Setoguchi","year":"2008","journal-title":"Science"},{"key":"10.1016\/j.immuni.2020.10.024_bib84","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1084\/jem.185.4.731","article-title":"Induction of the early growth response (Egr) family of transcription factors during thymic selection","volume":"185","author":"Shao","year":"1997","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib85","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/imr.12208","article-title":"Transcriptional and epigenetic networks of helper T and innate lymphoid cells","volume":"261","author":"Shih","year":"2014","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.immuni.2020.10.024_bib86","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib87","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev.immunol.21.120601.141107","article-title":"Positive and negative selection of T\u00a0cells","volume":"21","author":"Starr","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib88","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/ni.2897","article-title":"TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T\u00a0cell fate and interact with Runx3 to silence Cd4 in CD8(+) T\u00a0cells","volume":"15","author":"Steinke","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib89","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1146\/annurev-immunol-020711-075035","article-title":"Selection of self-reactive T\u00a0cells in the thymus","volume":"30","author":"Stritesky","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib90","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1073\/pnas.1217532110","article-title":"Murine thymic selection quantified using a unique method to capture deleted T\u00a0cells","volume":"110","author":"Stritesky","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.immuni.2020.10.024_bib91","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.immuni.2020.10.024_bib92","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni1183","article-title":"The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T\u00a0cell positive selection","volume":"6","author":"Sun","year":"2005","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib93","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1002\/eji.1830230326","article-title":"CD69 expression during selection and maturation of CD4+8+ thymocytes","volume":"23","author":"Swat","year":"1993","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib94","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1146\/annurev-immunol-042617-053411","article-title":"CD4 helper and CD8 cytotoxic T\u00a0cell differentiation","volume":"36","author":"Taniuchi","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib95","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib96","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1084\/jem.20171221","article-title":"Cbf\u03b22 controls differentiation of and confers homing capacity to prethymic progenitors","volume":"215","author":"Tenno","year":"2018","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib97","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.immuni.2020.10.024_bib98","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1126\/science.1831564","article-title":"Thymocyte expression of RAG-1 and RAG-2: termination by T\u00a0cell receptor cross-linking","volume":"253","author":"Turka","year":"1991","journal-title":"Science"},{"key":"10.1016\/j.immuni.2020.10.024_bib99","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1084\/jem.20040643","article-title":"CCR7 signals are essential for cortex-medulla migration of developing thymocytes","volume":"200","author":"Ueno","year":"2004","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib100","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.immuni.2008.09.019","article-title":"The zinc finger transcription factor Zbtb7b represses CD8-lineage gene expression in peripheral CD4+ T\u00a0cells","volume":"29","author":"Wang","year":"2008","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib101","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/ni.1647","article-title":"Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4(+) T\u00a0cells","volume":"9","author":"Wang","year":"2008","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib102","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.immuni.2011.08.007","article-title":"Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T\u00a0cell types","volume":"35","author":"Wei","year":"2011","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2020.10.024_bib104","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/ni767","article-title":"TOX: an HMG box protein implicated in the regulation of thymocyte selection","volume":"3","author":"Wilkinson","year":"2002","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib105","doi-asserted-by":"crossref","first-page":"e18270","DOI":"10.7554\/eLife.18270","article-title":"MYC activation and BCL2L11 silencing by a tumour virus through the large-scale reconfiguration of enhancer-promoter hubs","volume":"5","author":"Wood","year":"2016","journal-title":"eLife"},{"key":"10.1016\/j.immuni.2020.10.024_bib106","doi-asserted-by":"crossref","first-page":"7731","DOI":"10.1073\/pnas.1232420100","article-title":"Runx3 and Runx1 are required for CD8 T\u00a0cell development during thymopoiesis","volume":"100","author":"Woolf","year":"2003","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"10.1016\/j.immuni.2020.10.024_bib107","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/ni.3419","article-title":"Late stages of T\u00a0cell maturation in the thymus involve NF-\u03baB and tonic type I interferon signaling","volume":"17","author":"Xing","year":"2016","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib108","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.coi.2012.02.002","article-title":"CD4-CD8 differentiation in the thymus: connecting circuits and building memories","volume":"24","author":"Xiong","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib109","doi-asserted-by":"crossref","first-page":"7358","DOI":"10.4049\/jimmunol.179.11.7358","article-title":"CCR7 expression in developing thymocytes is linked to the CD4 versus CD8 lineage decision","volume":"179","author":"Yin","year":"2007","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2020.10.024_bib110","doi-asserted-by":"crossref","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":"10.1016\/j.immuni.2020.10.024_bib111","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1084\/jem.20092024","article-title":"The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T\u00a0cell differentiation in the thymus","volume":"206","author":"Zamisch","year":"2009","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2020.10.024_bib112","doi-asserted-by":"crossref","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-seq (MACS)","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome Biol."},{"key":"10.1016\/j.immuni.2020.10.024_bib113","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/344742a0","article-title":"Beta 2-microglobulin deficient mice lack CD4-8+ cytolytic T\u00a0cells","volume":"344","author":"Zijlstra","year":"1990","journal-title":"Nature"}],"container-title":["Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1074761320304659?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1074761320304659?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T08:11:32Z","timestamp":1761034292000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1074761320304659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":113,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["S1074761320304659"],"URL":"https:\/\/doi.org\/10.1016\/j.immuni.2020.10.024","relation":{},"ISSN":["1074-7613"],"issn-type":[{"value":"1074-7613","type":"print"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"An Integrated Epigenomic and Transcriptomic Map of Mouse and Human \u03b1\u03b2 T Cell Development","name":"articletitle","label":"Article Title"},{"value":"Immunity","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.immuni.2020.10.024","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}