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To address this challenge, we developed Rag1\u2011mediated time-stamp tracing, a genetic strategy that enables time\u2011resolved tracking of T\u2011cell developmental origins. We validate the specificity and temporal resolution of this approach across multiple analytical platforms, including flow cytometry, imaging, and single\u2011cell multiomics. Applying this strategy to thymic regulatory T (Treg) cell development, we show that time-stamp tracing resolves distinct phases of Treg cell induction, maturation, and long\u2011term adaptation within heterogeneous populations. This analysis identifies precursor populations for thymic Treg cell induction, uncovers a maturation program in nascent Treg cells marked by CD73 upregulation and progressive DNA hypomethylation at Treg cell\u2013specific loci, and distinguishes long\u2011lived mature Treg cells characterized by activation and clonal expansion. Together, these findings establish Rag1\u2011based time-stamp tracing as a versatile and unbiased approach for resolving T\u2011cell developmental origins across immunological contexts.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag154","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:46:38Z","timestamp":1785476798000},"source":"Crossref","is-referenced-by-count":1,"title":["Rag1-based time-stamp tracing of T-cell developmental origins"],"prefix":"10.1093","volume":"215","author":[{"given":"Menglin","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Immunology, St. Jude Children\u2019s Research Hospital , Memphis, TN,","place":["United States"]},{"name":"College of Graduate Health Sciences, University of Tennessee Health Science Center , Memphis, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of 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