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Immunol."],"published-print":{"date-parts":[[2026,3,13]]},"abstract":"<jats:p>\n                    To access the earliest stages of murine T cell development, we adapted a serum-free expansion system for hematopoietic stem and progenitor-like cells. These cells undergo normal T cell differentiation in vivo and in vitro, verified by gene expression trajectories from single-cell RNA sequencing. Their absolute differentiation speed is slower than that of fresh progenitors but is modulated with Flt3L priming. Leveraging this system, the earliest T cell lineage\u2013initiating events in response to Notch signaling included chromatin opening and transcriptional activation of the TCR-C\u03b2 locus. Acute CRISPR knockouts revealed that some transcription factors normally inherited from bone marrow progenitors impede early T cell development, with differing effects on proliferation. Among 23 factors tested,\n                    <jats:italic toggle=\"yes\">Lmo2<\/jats:italic>\n                    knockout greatly accelerated the onset of germline TCR-C\u03b2 locus transcription and expression of\n                    <jats:italic toggle=\"yes\">Tcf7<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Gata3<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">Runx1<\/jats:italic>\n                    and their targets. Thus, normal endogenous expression of this progenitor- and leukemia-associated factor markedly restrains T cell program initiation.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.adw7765","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:58:56Z","timestamp":1773424736000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["T cell development from expanded hematopoietic progenitors reveals initiation control by\n                    <i>Lmo2<\/i>\n                    and Flt3L priming"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7926-5527","authenticated-orcid":true,"given":"Boyoung","family":"Shin","sequence":"first","affiliation":[{"name":"Division of Biology &amp; Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA."},{"name":"Department of Microbiology and Immunology, Emory University School of 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