{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T11:31:31Z","timestamp":1773142291983,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,5]]},"group-title":"Immunology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI159457"],"award-info":[{"award-number":["AI159457"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Innate-like lymphocyte subsets are generated predominantly during early-life windows, yet the mechanisms that restrict their development in adulthood remain unclear. Here we identify\n                  <jats:italic>Cbfb2<\/jats:italic>\n                  gene dosage as a quantitative regulator of stage-specific lymphoid potential. We show that reduction of CBF\u03b22 levels unlocks fetal-like competence in adult hematopoietic progenitors, enabling robust generation of IL-17\u2013producing \u03b3\u03b4 T (T\u03b3\u03b417) cells. Although\n                  <jats:italic>Cbfb2<\/jats:italic>\n                  haploinsufficiency minimally alters steady-state transcription, chromatin profiling of H3K4me3 revealed promoter-level changes in adult lymphoid-primed multipotent progenitors consistent with altered developmental priming. In adult bone marrow chimeras,\n                  <jats:italic>Cbfb<\/jats:italic>\n                  <jats:sup>\n                    +\n                    <jats:italic>\/2m<\/jats:italic>\n                  <\/jats:sup>\n                  progenitors efficiently generated functional V\u03b32\n                  <jats:sup>+<\/jats:sup>\n                  T\u03b3\u03b417 cells in lymph nodes and skin, and restoring\n                  <jats:italic>Cbfb2<\/jats:italic>\n                  expression suppressed this capacity, establishing a dosage-dependent mechanism. Using an optimized in utero transplantation system, we further demonstrate that fetal niches amplify this latent competence and selectively favor IL-17\u2013committed \u03b3\u03b4 T cell differentiation over conventional \u03b1\u03b2 T cell output.\n                  <jats:italic>Notch1<\/jats:italic>\n                  haploinsufficiency enhanced T\u03b3\u03b417 generation and phenocopied the effect of CBF\u03b22 dosage reduction, linking quantitative NOTCH1 signaling to innate-like lymphocyte developmental programming. Together, these findings reveal that fetal versus adult lymphopoiesis is governed by quantitative tuning of RUNX:CBF\u03b2 activity and uncover unexpected plasticity in adult hematopoiesis controlled by transcription factor dosage.\n                <\/jats:p>","DOI":"10.64898\/2026.03.02.708762","type":"posted-content","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:30:12Z","timestamp":1772710212000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Cbfb2<\/i>\n                  gene dosage programs the differential lymphoid lineage developmental potential of fetal and adult hematopoietic progenitors"],"prefix":"10.64898","author":[{"given":"Alyssa","family":"Berthelette","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaelie","family":"Newell","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quan","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Taniuchi","sequence":"additional","affiliation":[{"name":"Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joonsoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Frascoli","sequence":"additional","affiliation":[{"name":"Department of Pathology, University 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