{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:45:47Z","timestamp":1792665947335,"version":"4.5.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"28","license":[{"start":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T00:00:00Z","timestamp":1561075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["U19 CCHI grant"],"award-info":[{"award-number":["U19 CCHI grant"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 AI030048"],"award-info":[{"award-number":["RO1 AI030048"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["Division of Intramural Research"],"award-info":[{"award-number":["Division of Intramural Research"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,7,9]]},"abstract":"<jats:p>\n                    We have recently defined a novel population of PD-1 (programmed cell death 1)+ TCF1 (T cell factor 1)+ virus-specific CD8 T cells that function as resource cells during chronic LCMV infection and provide the proliferative burst seen after PD-1 blockade. Such CD8 T cells have been found in other chronic infections and also in cancer in mice and humans. These CD8 T cells exhibit stem-like properties undergoing self-renewal and also differentiating into the terminally exhausted CD8 T cells. Here we compared the epigenetic signature of stem-like CD8 T cells with exhausted CD8 T cells. ATAC-seq analysis showed that stem-like CD8 T cells had a unique signature implicating activity of HMG (TCF) and RHD (NF-\u03baB) transcription factor family members in contrast to higher accessibility to ETS and RUNX motifs in exhausted CD8 T cells. In addition, regulatory regions of the transcription factors\n                    <jats:italic>Tcf7<\/jats:italic>\n                    and\n                    <jats:italic>Id3<\/jats:italic>\n                    were more accessible in stem-like cells whereas\n                    <jats:italic>Prdm1<\/jats:italic>\n                    and\n                    <jats:italic>Id2<\/jats:italic>\n                    were more accessible in exhausted CD8 T cells. We also compared the epigenetic signatures of the 2 CD8 T cell subsets from chronically infected mice with effector and memory CD8 T cells generated after an acute LCMV infection. Both CD8 T cell subsets generated during chronic infection were strikingly different from CD8 T cell subsets from acute infection. Interestingly, the stem-like CD8 T cell subset from chronic infection, despite sharing key functional properties with memory CD8 T cells, had a very distinct epigenetic program. These results show that the chronic stem-like CD8 T cell program represents a specific adaptation of the T cell response to persistent antigenic stimulation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1903520116","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T20:06:12Z","timestamp":1561147572000},"page":"14113-14118","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":227,"title":["Epigenetic signature of PD-1+ TCF1+ CD8 T cells that act as resource cells during chronic viral infection and respond to PD-1 blockade"],"prefix":"10.1073","volume":"116","author":[{"given":"Rohit R.","family":"Jadhav","sequence":"first","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305;"},{"name":"Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA 94306;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Jin","family":"Im","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305;"},{"name":"Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA 94306;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Xin","family":"Lin","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren J.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1409-3095","authenticated-orcid":false,"given":"William J.","family":"Greenleaf","sequence":"additional","affiliation":[{"name":"Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305;"},{"name":"Department of Genetics, Stanford University, Stanford, CA 94305;"},{"name":"Department of Applied Physics, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorg J.","family":"Goronzy","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305;"},{"name":"Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA 94306;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,6,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry E. J.","year":"2011","unstructured":"E. J. Wherry, T cell exhaustion. Nat. Immunol. 12, 492\u2013499 (2011).","journal-title":"Nat. Immunol."},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1084\/jem.188.12.2205","article-title":"Viral immune evasion due to persistence of activated T cells without effector function","volume":"188","author":"Zajac A. J.","year":"1998","unstructured":"A. J. Zajac ., Viral immune evasion due to persistence of activated T cells without effector function. J. Exp. Med. 188, 2205\u20132213 (1998).","journal-title":"J. Exp. Med."},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1084\/jem.187.9.1383","article-title":"Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes","volume":"187","author":"Gallimore A.","year":"1998","unstructured":"A. Gallimore ., Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes. J. Exp. Med. 187, 1383\u20131393 (1998).","journal-title":"J. Exp. Med."},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1128\/JVI.75.5.2458-2461.2001","article-title":"Functional impairment of simian immunodeficiency virus-specific CD8+ T cells during the chronic phase of infection","volume":"75","author":"Vogel T. U.","year":"2001","unstructured":"T. U. Vogel, T. M. Allen, J. D. Altman, D. I. Watkins, Functional impairment of simian immunodeficiency virus-specific CD8+ T cells during the chronic phase of infection. J. Virol. 75, 2458\u20132461 (2001).","journal-title":"J. Virol."},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1128\/JVI.77.5.3077-3083.2003","article-title":"Differential impairment of lytic and cytokine functions in senescent human immunodeficiency virus type 1-specific cytotoxic T lymphocytes","volume":"77","author":"Dagarag M.","year":"2003","unstructured":"M. Dagarag, H. Ng, R. Lubong, R. B. Effros, O. O. Yang, Differential impairment of lytic and cytokine functions in senescent human immunodeficiency virus type 1-specific cytotoxic T lymphocytes. J. Virol. 77, 3077\u20133083 (2003).","journal-title":"J. Virol."},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1146\/annurev-med-012017-043208","article-title":"CD8 T cell exhaustion in chronic infection and cancer: Opportunities for interventions","volume":"69","author":"Hashimoto M.","year":"2018","unstructured":"M. Hashimoto ., CD8 T cell exhaustion in chronic infection and cancer: Opportunities for interventions. Annu. Rev. Med. 69, 301\u2013318 (2018).","journal-title":"Annu. Rev. Med."},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.it.2015.02.008","article-title":"Overcoming T cell exhaustion in infection and cancer","volume":"36","author":"Pauken K. E.","year":"2015","unstructured":"K. E. Pauken, E. J. Wherry, Overcoming T cell exhaustion in infection and cancer. Trends Immunol. 36, 265\u2013276 (2015).","journal-title":"Trends Immunol."},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1126\/science.aaa8172","article-title":"The future of immune checkpoint therapy","volume":"348","author":"Sharma P.","year":"2015","unstructured":"P. Sharma, J. P. Allison, The future of immune checkpoint therapy. Science 348, 56\u201361 (2015).","journal-title":"Science"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"Barber D. L.","year":"2006","unstructured":"D. L. Barber ., Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439, 682\u2013687 (2006).","journal-title":"Nature"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/ni.1679","article-title":"Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection","volume":"10","author":"Blackburn S. D.","year":"2009","unstructured":"S. D. Blackburn ., Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10, 29\u201337 (2009).","journal-title":"Nat. Immunol."},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nature07662","article-title":"Enhancing SIV-specific immunity in vivo by PD-1 blockade","volume":"458","author":"Velu V.","year":"2009","unstructured":"V. Velu ., Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature 458, 206\u2013210 (2009).","journal-title":"Nature"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.coi.2013.03.003","article-title":"Manipulating the PD-1 pathway to improve immunity","volume":"25","author":"Kamphorst A. O.","year":"2013","unstructured":"A. O. Kamphorst, R. Ahmed, Manipulating the PD-1 pathway to improve immunity. Curr. Opin. Immunol. 25, 381\u2013388 (2013).","journal-title":"Curr. Opin. Immunol."},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.intimp.2018.06.001","article-title":"Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors","volume":"62","author":"Hargadon K. M.","year":"2018","unstructured":"K. M. Hargadon, C. E. Johnson, C. J. Williams, Immune checkpoint blockade therapy for cancer: An overview of FDA-approved immune checkpoint inhibitors. Int. Immunopharmacol. 62, 29\u201339 (2018).","journal-title":"Int. Immunopharmacol."},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"Im S. J.","year":"2016","unstructured":"S. J. Im ., Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417\u2013421 (2016).","journal-title":"Nature"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nature19317","article-title":"Follicular CXCR5-expressing CD8(+) T cells curtail chronic viral infection","volume":"537","author":"He R.","year":"2016","unstructured":"R. He ., Follicular CXCR5-expressing CD8(+) T cells curtail chronic viral infection. Nature 537, 412\u2013428 (2016).","journal-title":"Nature"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.immuni.2016.07.021","article-title":"T cell factor 1-expressing memory-like CD8(+) T cells sustain the immune response to chronic viral infections","volume":"45","author":"Utzschneider D. T.","year":"2016","unstructured":"D. T. Utzschneider ., T cell factor 1-expressing memory-like CD8(+) T cells sustain the immune response to chronic viral infections. Immunity 45, 415\u2013427 (2016).","journal-title":"Immunity"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"eaai8593","DOI":"10.1126\/sciimmunol.aai8593","article-title":"The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness","volume":"1","author":"Wu T.","year":"2016","unstructured":"T. Wu ., The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness. Sci. Immunol. 1, eaai8593 (2016).","journal-title":"Sci. Immunol."},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/ni.3543","article-title":"CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles","volume":"17","author":"Leong Y. A.","year":"2016","unstructured":"Y. A. Leong ., CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles. Nat. Immunol. 17, 1187\u20131196 (2016).","journal-title":"Nat. Immunol."},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"e1005924","DOI":"10.1371\/journal.ppat.1005924","article-title":"Follicular regulatory CD8 T cells impair the germinal center response in SIV and ex vivo HIV infection","volume":"12","author":"Miles B.","year":"2016","unstructured":"B. Miles ., Follicular regulatory CD8 T cells impair the germinal center response in SIV and ex vivo HIV infection. PLoS Pathog. 12, e1005924 (2016).","journal-title":"PLoS Pathog."},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1073\/pnas.1621418114","article-title":"Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection","volume":"114","author":"Mylvaganam G. H.","year":"2017","unstructured":"G. H. Mylvaganam ., Dynamics of SIV-specific CXCR5+ CD8 T cells during chronic SIV infection. Proc. Natl. Acad. Sci. U.S.A. 114, 1976\u20131981 (2017).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"eaag2285","DOI":"10.1126\/scitranslmed.aag2285","article-title":"Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies","volume":"9","author":"Petrovas C.","year":"2017","unstructured":"C. Petrovas ., Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. Sci. Transl. Med. 9, eaag2285 (2017).","journal-title":"Sci. Transl. Med."},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.cell.2018.10.038","article-title":"Defining T cell states associated with response to checkpoint immunotherapy in melanoma","volume":"175","author":"Sade-Feldman M.","year":"2018","unstructured":"M. Sade-Feldman ., Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell 175, 998\u20131013.e20 (2018).","journal-title":"Cell"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.immuni.2018.12.021","article-title":"Intratumoral Tcf1(+)PD-1(+)CD8(+) T cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy","volume":"50","author":"Siddiqui I.","year":"2019","unstructured":"I. Siddiqui ., Intratumoral Tcf1(+)PD-1(+)CD8(+) T cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy. Immunity 50, 195\u2013211.e10 (2019).","journal-title":"Immunity"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/s41590-019-0312-6","article-title":"Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade","volume":"20","author":"Miller B. C.","year":"2019","unstructured":"B. C. Miller ., Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Nat. Immunol. 20, 326\u2013336 (2019).","journal-title":"Nat. Immunol."},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nri.2017.146","article-title":"Epigenetic control of CD8+ T cell differentiation","volume":"18","author":"Henning A. N.","year":"2018","unstructured":"A. N. Henning, R. Roychoudhuri, N. P. Restifo, Epigenetic control of CD8+ T cell differentiation. Nat. Rev. Immunol. 18, 340\u2013356 (2018).","journal-title":"Nat. Rev. Immunol."},{"key":"e_1_3_4_26_2","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 J. D.","year":"2013","unstructured":"J. D. Buenrostro, P. G. Giresi, L. C. Zaba, H. Y. Chang, W. J. Greenleaf, Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213\u20131218 (2013).","journal-title":"Nat. Methods"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love M. I.","year":"2014","unstructured":"M. I. Love, W. Huber, S. Anders, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.aaf0683","article-title":"Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent","volume":"355","author":"Kamphorst A. O.","year":"2017","unstructured":"A. O. Kamphorst ., Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science 355, 1423\u20131427 (2017).","journal-title":"Science"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nri3307","article-title":"Transcriptional control of effector and memory CD8+ T cell differentiation","volume":"12","author":"Kaech S. M.","year":"2012","unstructured":"S. M. Kaech, W. Cui, Transcriptional control of effector and memory CD8+ T cell differentiation. Nat. Rev. Immunol. 12, 749\u2013761 (2012).","journal-title":"Nat. Rev. Immunol."},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/jnr.22562","article-title":"HeyL promotes neuronal differentiation of neural progenitor cells","volume":"89","author":"Jalali A.","year":"2011","unstructured":"A. Jalali ., HeyL promotes neuronal differentiation of neural progenitor cells. J. Neurosci. Res. 89, 299\u2013309 (2011).","journal-title":"J. Neurosci. Res."},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.immuni.2016.12.015","article-title":"SATB1 expression governs epigenetic repression of PD-1 in tumor-reactive T cells","volume":"46","author":"Stephen T. L.","year":"2017","unstructured":"T. L. Stephen ., SATB1 expression governs epigenetic repression of PD-1 in tumor-reactive T cells. Immunity 46, 51\u201364 (2017).","journal-title":"Immunity"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.immuni.2013.10.007","article-title":"Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation","volume":"39","author":"Yao S.","year":"2013","unstructured":"S. Yao ., Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation. Immunity 39, 833\u2013845 (2013).","journal-title":"Immunity"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.4049\/jimmunol.1000842","article-title":"STAT5 is critical to maintain effector CD8+ T cell responses","volume":"185","author":"Tripathi P.","year":"2010","unstructured":"P. Tripathi ., STAT5 is critical to maintain effector CD8+ T cell responses. J. Immunol. 185, 2116\u20132124 (2010).","journal-title":"J. Immunol."},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1038\/ncomms3830","article-title":"A genome-wide regulatory network identifies key transcription factors for memory CD8+ T-cell development","volume":"4","author":"Hu G.","year":"2013","unstructured":"G. Hu, J. Chen, A genome-wide regulatory network identifies key transcription factors for memory CD8+ T-cell development. Nat. Commun. 4, 2830 (2013).","journal-title":"Nat. Commun."},{"key":"e_1_3_4_35_2","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 A. E.","year":"2011","unstructured":"A. E. Moran ., T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J. Exp. Med. 208, 1279\u20131289 (2011).","journal-title":"J. Exp. Med."},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/369648a0","article-title":"Cytotoxic T-cell memory without antigen","volume":"369","author":"Lau L. L.","year":"1994","unstructured":"L. L. Lau, B. D. Jamieson, T. Somasundaram, R. Ahmed, Cytotoxic T-cell memory without antigen. Nature 369, 648\u2013652 (1994).","journal-title":"Nature"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/ni1009","article-title":"Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells","volume":"4","author":"Kaech S. M.","year":"2003","unstructured":"S. M. Kaech ., Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat. Immunol. 4, 1191\u20131198 (2003).","journal-title":"Nat. Immunol."},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1084\/jem.20071641","article-title":"Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates","volume":"205","author":"Sarkar S.","year":"2008","unstructured":"S. Sarkar ., Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. J. Exp. Med. 205, 625\u2013640 (2008).","journal-title":"J. Exp. Med."},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.immuni.2007.07.010","article-title":"Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor","volume":"27","author":"Joshi N. S.","year":"2007","unstructured":"N. S. Joshi ., Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity 27, 281\u2013295 (2007).","journal-title":"Immunity"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/nature25144","article-title":"Effector CD8 T cells dedifferentiate into long-lived memory cells","volume":"552","author":"Youngblood B.","year":"2017","unstructured":"B. Youngblood ., Effector CD8 T cells dedifferentiate into long-lived memory cells. Nature 552, 404\u2013409 (2017).","journal-title":"Nature"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nature24633","article-title":"Origin and differentiation of human memory CD8 T cells after vaccination","volume":"552","author":"Akondy R. S.","year":"2017","unstructured":"R. S. Akondy ., Origin and differentiation of human memory CD8 T cells after vaccination. Nature 552, 362\u2013367 (2017).","journal-title":"Nature"},{"key":"e_1_3_4_42_2","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 S.","year":"2010","unstructured":"S. Heinz ., Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576\u2013589 (2010).","journal-title":"Mol. Cell"},{"key":"e_1_3_4_43_2","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 A. N.","year":"2017","unstructured":"A. N. Schep, B. Wu, J. D. Buenrostro, W. J. Greenleaf, chromVAR: Inferring transcription-factor-associated accessibility from single-cell epigenomic data. Nat. Methods 14, 975\u2013978 (2017).","journal-title":"Nat. Methods"},{"key":"e_1_3_4_44_2","unstructured":"R Core Team R: A Language and Environment for Statistical Computing (Version 3.5.2 R Foundation for Statistical Computing Vienna Austria 2018). https:\/\/www.R-project.org\/."},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nbt.1630","article-title":"GREAT improves functional interpretation of cis-regulatory regions","volume":"28","author":"McLean C. Y.","year":"2010","unstructured":"C. Y. McLean ., GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28, 495\u2013501 (2010).","journal-title":"Nat. Biotechnol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1903520116","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1903520116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T15:27:54Z","timestamp":1654615674000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1903520116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,21]]},"references-count":45,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2019,7,9]]}},"alternative-id":["10.1073\/pnas.1903520116"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1903520116","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.736033074.793570394","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,21]]},"assertion":[{"value":"2019-06-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}