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In contrast to adult cells, naïve neonatal cells exhibit a greatly limited ability to differentiate into memory cells, a fundamental property of their adult counterparts. Here, we describe the role of the miR-29 microRNA in naïve T cells, focusing on age-related differences in miR-29 expression and the consequences of these differences in adult and neonatal cells, from mice and humans. In adults, high expression of miR-29 licenses naïve cells towards eventual memory cell fates whereas neonatal naïve cells, which lack high expression of miR-29, are predisposed towards effector cell fates in response to an infection. Multiple lines of evidence support this model, including analysis of a mouse model deficient in miR-29, which we examine with adoptive transfer experiments to define the functional consequences of reduction of miR-29, together with genomic assays to define the regulatory impact of miR-29. Adult miR 29 deficient naïve CD8+ T cells cell are primed for activation and therefore secrete elevated levels of cytolytic molecules, and express transcription factors at levels associated with effector cell differentiation moreover, these cells exhibit an altered CD8+ T cell memory repertoire, akin to that of neonatal CD8+ T cells. Importantly, we use a method that exploits extracellular vesicles as a delivery vehicle with which to modulate levels of miR-29 in neonatal and adult naïve T cells, examining both human and mouse cells. For example, increasing miR 29 expression in mouse naïve neonatal CD8+ T cells significantly improved the memory response during infection, concomitant with alterations to the chromatin landscape characteristic of cells primed for memory differentiation. Delivery of miR-29 antagomirs to human adult naïve CD8+ T cells was sufficient to induce the adult cells to adopt phenotypes and gene expression signatures normally found in cells present in newborns. This study establishes miR-29 as a key conserved regulator in naïve CD8+ T cells, and by adjusting levels of miR-29, has the potential to underlie therapeutic strategies for controlling the balance of effector versus memory fates in human T cells. Overall design: mRNA profiles of true naïve(TN) and virtual memory(VM) adult CD8+ T cells, neonatal CD8+ T cells and neonatal CD8+ T cells with miR-29 levels induced."],"tag":["xref:PubMed:34758312"],"repository":["ENA"],"description_synonyms":["HH, Regulations, Thymus-Dependent Lymphocytes, Laboratory, Mus domesticus, bar, RNA-seq., T-Lymphocyte, IDOL, House Mouse, Social Controls, Hh, anon-WO0134654.19, DmelCG4637, T Lymphocyte, House, Mus musculus domesticus, Whole Transcriptome Shotgun Sequencing, Mir, MIR, MAL, immature T cell, Mice, Formal Social Controls, Miranda, Immune Processes, Immune Responses, MONDOA, Swiss, T-Cells, Mrt, T, Swiss Mice, mir, Social, T Cells, Myosin regulatory light chain-interacting protein, Immune Response, Immune, bar-3, mature T cell, bHLHe36, house mouse, Immune Process, Idol, T Lymphocytes, Thymus Dependent Lymphocytes, Lymphocyte, 9430057C20Rik, l(3)hh, Process, Formal Social Control, Myosin regulatory light chain interacting protein, RnBP, 6.3.2.-, mouse, Leu2, GlcNAc 2-epimerase, Cell, mice C57BL/6xCBA/CaJ hybrid, CG4637, Mus muscaris, CG12249, AW228700, N-acetyl-D-glucosamine 2-epimerase, Social Control, T-Cell, Mus, RENBP, bar3, DmelCG12249, T lymphocyte, Mus musculus, T-cell, l(3)neo56, l(3)neo57, mice, p32, Mira, Thymus-Dependent, Swiss Mouse, Control, Lymphocytes, House Mice, Inducible degrader of the LDL-receptor, Controls, T-lymphocyte, Thymus-Dependent Lymphocyte, AGE, domesticus, Laboratory Mice, T cell, anon-WO0182946.19, Cells, MIRA, Response, renin-binding protein, regulation, T Cell, Mouse, CD8, Regulation, Laboratory Mouse, hg"],"name_synonyms":["HH, Regulations, Thymus-Dependent Lymphocytes, Laboratory, Mus domesticus, bar, RNA-seq., T-Lymphocyte, IDOL, House Mouse, Social Controls, Hh, anon-WO0134654.19, DmelCG4637, T Lymphocyte, House, Mus musculus domesticus, Whole Transcriptome Shotgun Sequencing, Mir, MIR, MAL, immature T cell, Mice, Formal Social Controls, Miranda, Immune Processes, Immune Responses, MONDOA, Swiss, T-Cells, Mrt, T, Swiss Mice, mir, Social, T Cells, Myosin regulatory light chain-interacting protein, Immune Response, Immune, bar-3, mature T cell, bHLHe36, house mouse, Immune Process, Idol, T Lymphocytes, Thymus Dependent Lymphocytes, Lymphocyte, 9430057C20Rik, l(3)hh, Process, Formal Social Control, Myosin regulatory light chain interacting protein, RnBP, 6.3.2.-, mouse, Leu2, GlcNAc 2-epimerase, Cell, mice C57BL/6xCBA/CaJ hybrid, CG4637, Mus muscaris, CG12249, AW228700, N-acetyl-D-glucosamine 2-epimerase, Social Control, T-Cell, Mus, RENBP, bar3, DmelCG12249, T lymphocyte, Mus musculus, T-cell, l(3)neo56, l(3)neo57, mice, p32, Mira, Thymus-Dependent, Swiss Mouse, Control, Lymphocytes, House Mice, Inducible degrader of the LDL-receptor, Controls, T-lymphocyte, Thymus-Dependent Lymphocyte, AGE, domesticus, Laboratory Mice, T cell, anon-WO0182946.19, Cells, MIRA, Response, renin-binding protein, regulation, T Cell, Mouse, CD8, Regulation, Laboratory Mouse, hg"],"additional_accession":[]},"is_claimable":false,"name":"Developmental regulation by miR-29 specifies age-related differences in the CD8+ T cell immune response (Mouse RNA-Seq)","description":"Developmental regulation by miR-29 specifies age-related differences in the CD8+ T cell immune response (Mouse RNA-Seq)","dates":{"last_updated":"2025-09-24","first_public":"2021-11-10"},"accession":"PRJNA670190","cross_references":{"GEO":["GSE159686"],"taxon":["10090"],"PubMed":["34758312"]}}