{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["11(34)"],"submitter":["Lynch AC"],"pubmed_abstract":["Memory CD8 T cells provide long-lasting immunity, but their developmental origins remain incompletely defined. Growing evidence suggests that functional heterogeneity exists within the naïve T cell pool, shaping lineage potential before antigen stimulation. Here, we identify a subpopulation of naïve CD8 T cells expressing death-associated protein-like 1 (Dapl1) that contains preprogrammed precursors biased toward memory differentiation. The differentiation of these precursors is independent of Dapl1 but relies on the transcription factor B-cell lymphoma/leukaemia 11b (Bcl11b), resulting in the generation of Dapl1+ central memory-like CD8 T cells after infection and stem-like memory cells in cancer. Dapl1+ naïve T cells originate among mature thymocytes and gradually appear in the periphery postnatally. Peripheral Dapl1+ and Dapl1- populations show limited plasticity, supporting a thymic-imprinting model. These findings reveal a developmentally imprinted subset of naïve CD8 T cells committed to memory fate, uncovering an alternative pathway for memory T cell generation offering new avenues for therapeutic application."],"journal":["Science advances"],"pagination":["eadx5687"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12372879"],"repository":["biostudies-literature"],"pubmed_title":["A Dapl1<sup>+</sup> subpopulation of naive CD8 T cells is enriched for memory-lineage precursors."],"pmcid":["PMC12372879"],"pubmed_authors":["Alfandari D","Liang X","Cui W","Hioki KA","Thesmar I","Cernjul J","He XD","Mager J","Pobezinsky LA","Lynch AC","Pobezinskaya EL"],"additional_accession":[]},"is_claimable":false,"name":"A Dapl1<sup>+</sup> subpopulation of naive CD8 T cells is enriched for memory-lineage precursors.","description":"Memory CD8 T cells provide long-lasting immunity, but their developmental origins remain incompletely defined. Growing evidence suggests that functional heterogeneity exists within the naïve T cell pool, shaping lineage potential before antigen stimulation. Here, we identify a subpopulation of naïve CD8 T cells expressing death-associated protein-like 1 (Dapl1) that contains preprogrammed precursors biased toward memory differentiation. The differentiation of these precursors is independent of Dapl1 but relies on the transcription factor B-cell lymphoma/leukaemia 11b (Bcl11b), resulting in the generation of Dapl1+ central memory-like CD8 T cells after infection and stem-like memory cells in cancer. Dapl1+ naïve T cells originate among mature thymocytes and gradually appear in the periphery postnatally. Peripheral Dapl1+ and Dapl1- populations show limited plasticity, supporting a thymic-imprinting model. These findings reveal a developmentally imprinted subset of naïve CD8 T cells committed to memory fate, uncovering an alternative pathway for memory T cell generation offering new avenues for therapeutic application.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-05-09T10:44:41.127Z","creation":"2026-04-08T00:48:23.743Z"},"accession":"S-EPMC12372879","cross_references":{"pubmed":["40845112"],"doi":["10.1126/sciadv.adx5687"]}}