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Based on the expression of \u03b1\u03b2 and \u03b3\u03b4 receptors, T cells are mainly divided into \u03b1\u03b2 and \u03b3\u03b4 T cells. In the thymus, they share common progenitor cells, while undergoing a series of well\u2010characterized and different developmental processes. <jats:italic>N<\/jats:italic><jats:sup>6<\/jats:sup>\u2010Methyladenosine (m<jats:sup>6<\/jats:sup>A), one of the most abundant modifications in mRNAs, plays critical roles in cell development and maintenance of function. Recently, we have demonstrated that the depletion of m<jats:sup>6<\/jats:sup>A demethylase ALKBH5 in lymphocytes specifically induces an expansion of \u03b3\u03b4 T cells through the regulation of Jag1\/Notch2 signaling, but not \u03b1\u03b2 T cells, indicating a checkpoint role of ALKBH5 and m<jats:sup>6<\/jats:sup>A modification in the early development of \u03b3\u03b4 T cells. Based on previous studies, many key pathway molecules, which exert dominant roles in \u03b3\u03b4 T cell fate determination, have been identified as the targets regulated by m<jats:sup>6<\/jats:sup>A modification. In this review, we mainly summarize the potential regulation between m<jats:sup>6<\/jats:sup>A modification and these key signaling molecules in the \u03b3\u03b4 T cell lineage commitment, to provide new perspectives in the checkpoint of \u03b3\u03b4 T cell development.<\/jats:p>","DOI":"10.1002\/bies.202300002","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T10:09:56Z","timestamp":1679393396000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>N<sup>6<\/sup><\/i>\u2010 Methyladenosine defines a new checkpoint in \u03b3\u03b4 T cell development"],"prefix":"10.1002","volume":"45","author":[{"given":"Jiachen","family":"Zhao","sequence":"first","affiliation":[{"name":"Shanghai Institute of Immunology State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenbo","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Jiao Tong University School of Medicine\u2010Yale Institute for Immune Metabolism Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3573-6803","authenticated-orcid":false,"given":"Hua\u2010Bing","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology State Key Laboratory of Oncogenes and Related Genes Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Jiao Tong University School of Medicine\u2010Yale Institute for Immune Metabolism Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2993"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14760"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2820"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348\u20100421.1993.tb03207.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/342931a0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.24.9729"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13256"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/925135"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3442"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.03.002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3384"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2781"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.08.001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.71.10.3971"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1515\/bchm2.1982.363.1.33"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature20577"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07848"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.026"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax4468"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21671"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abl5723"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20100916\u2010x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.003"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11112"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010022\u201000534\u20100"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18434"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.041"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18298"},{"issue":"11","key":"e_1_2_9_31_1","first-page":"1233","article-title":"Purification and cDNA cloning of the AdoMet\u2010binding subunit of the human mRNA (N6\u2010adenosine)\u2010methyltransferase","volume":"3","author":"Bokar J. 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