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Replicative history marks transcriptional and functional disparity in the memory T cell pool II

ABSTRACT: To validate whether division history is linked to functional and transcriptional properties we established a CTV-based serial-transfer approach that allowes single cell transcriptional profiling of memory T cells that have undergone a high or low amount of prior division

ORGANISM(S): Mus musculus

PROVIDER: GSE184947 | GEO | 2022/01/31

REPOSITORIES: GEO

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Replicative history marks transcriptional and functional disparity in the memory T cell pool

Project description:Mice received DivisionRecorder+ or unmodified OT-I T cells and were challenged with LM-OVA. During memory phase we FACS sorted memory CD8+ OT-I T cells (and sub-sorted RFP+ and RFP- cells in the case of DivisionRecorder+ cells) from spleen material and performed single cell RNA sequencing.

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Replicative history marks transcriptional and functional disparity in the CD8<sup>+</sup> T cell memory pool.

Project description:Clonal expansion is a core aspect of T cell immunity. However, little is known with respect to the relationship between replicative history and the formation of distinct CD8+ memory T cell subgroups. To address this issue, we developed a genetic-tracing approach, termed the DivisionRecorder, that reports the extent of past proliferation of cell pools in vivo. Using this system to genetically 'record' the replicative history of different CD8+ T cell populations throughout a pathogen-specific immune response, we demonstrate that the central memory T (TCM) cell pool is marked by a higher number of prior divisions than the effector memory T cell pool, owing to the combination of strong proliferative activity during the acute immune response and selective proliferative activity after pathogen clearance. Furthermore, by combining DivisionRecorder analysis with single-cell transcriptomics and functional experiments, we show that replicative history identifies distinct cell pools within the TCM compartment. Specifically, we demonstrate that lowly divided TCM cells display enriched expression of stem-cell-associated genes, exist in a relatively quiescent state, and are superior in eliciting a proliferative recall response upon activation. These data provide the first evidence that a stem-cell-like memory T cell pool that reconstitutes the CD8+ T cell effector pool upon reinfection is marked by prior quiescence.

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Replicative history marks transcriptional and functional disparity in the memory T cell pool

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Replicative history marks transcriptional and functional disparity in the memory T cell pool II

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Project description:Just as animal monozygotic twins can experience different environmental conditions by being reared apart, individual genetically-identical trees of the genus Populus can also be exposed to contrasting environmental conditions by being grown in different locations. As such, clonally-propagated Populus trees provide an opportunity to interrogate the impact of individual environmental history on current response to environmental stimuli. To test the hypothesis that current responses to an environmental stimulus, drought, are contingent on environmental history, the transcriptome-level drought responses of three economically important hybrid genotypes: DN34 (Populus deltoides x P. nigra); Walker (P. deltoides var. occidentalis x (P. laurifolia x P. nigra)); and, Okanese (‘Walker’ x (P. laurifolia x P. nigra)) derived from two different locations were compared. Strikingly, differences in transcript abundance patterns in response to drought were based on differences in geographic origin of clones for two of the three genotypes. This observation was most pronounced for the genotypes with the longest time since establishment and last common propagation. Differences in genome-wide DNA methylation paralleled the transcriptome level trends, where the clones with the most divergent transcriptomes and clone history had the most marked differences in the extent of total DNA methylation, suggesting an epigenetic basis for the clone-history-dependent transcriptome divergence. The data provide insights into the interplay between genotype and environment in the ecologically and economically important Populus genus, with implications for both the industrial application of Populus trees, and the evolution and persistence of these important tree species. 72 arrays total. 2 time points. 2 water regimes. 3 biological replicates per treatment

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Clone History Shapes Populus Drought Responses

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