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Our previously generated transcriptomic datasets indicate that Stab2 is specifically expressed in the yolk sac but not the aortic endothelial cells. Leveraging this spatially restricted expression pattern, we generated a Stab2-CrexERT2 inducible genetic lineage tracing mouse model and demonstrated its ability to label yolk sac-derived hematopoietic cells in vivo. Importantly, we detected the contribution of the yolk sac endothelial cells labeled at embryonic day 9.5 to a subset of V\u03b31 \u03b3\u03b4 T cells in the adult liver but hardly to any hematopoietic progenitors in the thymus and bone marrow. Single-cell transcriptomic profiling combined with functional evaluation revealed that the Stab2-labeled yolk sac endothelial cell-derived hepatic \u03b3\u03b4 T cells preferentially enrich IFN-\u03b3-producing \u03b3\u03b4 T1 cells and overrepresent characteristics associated with tissue homeostasis and repair. Collectively, our findings provide direct in vivo evidence for the existence of a bone marrow hematopoietic stem cell-independent and thymus-independent developmental pathway of liver \u03b3\u03b4 T cells originating from yolk sac endothelial cells, and suggest that different origins and developmental paths may confer distinct functional properties to \u03b3\u03b4 T cells.<\/jats:p>","DOI":"10.1093\/procel\/pwag037","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:44:31Z","timestamp":1780055071000},"page":"922-933","source":"Crossref","is-referenced-by-count":0,"title":["A yolk sac-derived hepatic \u03b3\u03b4 T cell subpopulation develops in a hematopoietic stem cell- and thymus-independent manner"],"prefix":"10.1093","volume":"17","author":[{"given":"Yuzhe","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Institute of Hematology, School of Medicine, Jinan University , Guangzhou 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