GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE308nnn/GSE308060/primaryOK200TranscriptomicsMus musculus OtherExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308060GEOGSEfalseEpigenetic control of CD8+ T cell tissue resident memory precursors differentiation by the histone methyltransferase SUV39H1The molecular mechanisms of fate choices between circulatory and tissue-resident memory (TRM) cells upon CD8+ T cell activation, are still largely unknown. We show here that deletion of the histone methyltransferase SUV39H1 in CD8+ T cells, enhances homing to non-lymphoid tissues. At steady state, after space-induced proliferation or flu infection, SUV39H1-defective cells in tissues express CD49d and differentiate predominantly into CD69+/CD103- TRM. Persisting SUV39H1-defective T cells in lungs are protective in flu re-infection and lung tumor models. Accumulation of SUV39H1-deficient TRM cells is due to increased proportions of TRM precursors with high stemness and TRM precursor potential. We conclude that SUV39H1 restrains CD69+ CD103- TRM commitment by inhibiting memory and stemness programs during CD8+ T cells effector differentiation. These results encourage the use of SUV39H1 depletion in the context of adoptive T cell therapies to optimize both the efficiency of target cell eradication and the long-term persistence of memory cells.2026/09/14GSE308060GSM9237323GSM9237324GSM923732524247308060Mus musculus