{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:03:21Z","timestamp":1774418601271,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["637843"],"award-info":[{"award-number":["637843"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Autoimmune regulator\n                    <jats:sup>+<\/jats:sup>\n                    (Aire) medullary thymic epithelial cells (mTECs) play a critical role in tolerance induction. Several studies demonstrated that Aire\n                    <jats:sup>+<\/jats:sup>\n                    mTECs differentiate further into Post\u2010Aire cells. Yet, the identification of terminal stages of mTEC maturation depends on unique fate\u2010mapping mouse models. Herein, we resolve this limitation by segmenting the mTEC\n                    <jats:sup>hi<\/jats:sup>\n                    (MHCII\n                    <jats:sup>hi<\/jats:sup>\n                    CD80\n                    <jats:sup>hi<\/jats:sup>\n                    ) compartment into mTEC\n                    <jats:sup>A\/hi<\/jats:sup>\n                    (CD24\n                    <jats:sup>\u2212<\/jats:sup>\n                    Sca1\n                    <jats:sup>\u2212<\/jats:sup>\n                    ), mTEC\n                    <jats:sup>B\/hi<\/jats:sup>\n                    (CD24\n                    <jats:sup>+<\/jats:sup>\n                    Sca1\n                    <jats:sup>\u2212<\/jats:sup>\n                    ), and mTEC\n                    <jats:sup>C\/hi<\/jats:sup>\n                    (CD24\n                    <jats:sup>+<\/jats:sup>\n                    Sca1\n                    <jats:sup>+<\/jats:sup>\n                    ). While mTEC\n                    <jats:sup>A\/hi<\/jats:sup>\n                    included mostly Aire\u2010expressing cells, mTEC\n                    <jats:sup>B\/hi<\/jats:sup>\n                    contained Aire\n                    <jats:sup>+<\/jats:sup>\n                    and Aire\n                    <jats:sup>\u2212<\/jats:sup>\n                    cells and mTEC\n                    <jats:sup>C\/hi<\/jats:sup>\n                    were mainly composed of cells lacking Aire. The differential expression pattern of Aire led us to investigate the precursor\u2010product relationship between these subsets. Strikingly, transcriptomic analysis of mTEC\n                    <jats:sup>A\/hi<\/jats:sup>\n                    , mTEC\n                    <jats:sup>B\/hi<\/jats:sup>\n                    , and mTEC\n                    <jats:sup>C\/hi<\/jats:sup>\n                    sequentially mirrored the specific genetic program of Early\u2010, Late\u2010 and Post\u2010Aire mTECs. Corroborating their Post\u2010Aire nature, mTEC\n                    <jats:sup>C\/hi<\/jats:sup>\n                    downregulated the expression of tissue\u2010restricted antigens, acquired traits of differentiated keratinocytes, and were absent in Aire\u2010deficient mice. Collectively, our findings reveal a new and simple blueprint to survey late stages of mTEC differentiation.\n                  <\/jats:p>","DOI":"10.1002\/eji.202048764","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T15:10:25Z","timestamp":1599059425000},"page":"311-318","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A novel method to identify Post\u2010Aire stages of medullary thymic epithelial cell differentiation"],"prefix":"10.1002","volume":"51","author":[{"given":"Pedro","family":"Ferreirinha","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S) Universidade do Porto  Porto Portugal"},{"name":"Instituto de Biologia Molecular e Celular (IBMC) Universidade do Porto  Porto Portugal"}]},{"given":"Camila","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S) Universidade do Porto  Porto Portugal"},{"name":"Instituto de Biologia Molecular e Celular (IBMC) Universidade do Porto  Porto Portugal"}]},{"given":"Junko","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology Institute for Enzyme Research Tokushima University  Tokushima Japan"}]},{"given":"Jonathan J. M.","family":"Landry","sequence":"additional","affiliation":[{"name":"Genomics Core Facility European Molecular Biology Laboratory  Heidelberg Germany"}]},{"given":"Minoru","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology Institute for Enzyme Research Tokushima University  Tokushima Japan"}]},{"given":"Catarina","family":"Meireles","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S) Universidade do Porto  Porto Portugal"}]},{"given":"Andrea J.","family":"White","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy College of Medical and Dental Sciences Medical School University of Birmingham  Birmingham UK"}]},{"given":"Izumi","family":"Ohigashi","sequence":"additional","affiliation":[{"name":"Division of Experimental Immunology Institute of Advanced Medical Sciences University of Tokushima  Tokushima Japan"}]},{"given":"Leonor","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S) Universidade do Porto  Porto Portugal"},{"name":"Instituto de Biologia Molecular e Celular (IBMC) Universidade do Porto  Porto Portugal"}]},{"given":"Vladimir","family":"Benes","sequence":"additional","affiliation":[{"name":"Genomics Core Facility European Molecular Biology Laboratory  Heidelberg Germany"}]},{"given":"Yousuke","family":"Takahama","sequence":"additional","affiliation":[{"name":"National Cancer Institute NIH  Bethesda Maryland USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2917-4085","authenticated-orcid":false,"given":"Graham","family":"Anderson","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Immunotherapy College of Medical and Dental Sciences Medical School University of Birmingham  Birmingham UK"}]},{"given":"Mitsuru","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology Institute for Enzyme Research Tokushima University  Tokushima Japan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1567-8389","authenticated-orcid":false,"given":"Nuno L.","family":"Alves","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S) Universidade do Porto  Porto Portugal"},{"name":"Instituto de Biologia Molecular e Celular (IBMC) Universidade do Porto  Porto 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