Identification of age-related changes in gene expression and chromatin accessibility in T cells from thymus to periphery (60K)
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PROVIDER: PRJNA445876 | ENA |
REPOSITORIES: ENA
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Project description:Aging of immune system is characterized by progressive decline of physiological and cellular function of T cells. Recent studies of naïve T cells from young and old mice have identified age-related altered gene expressions but the mechanisms underlying age associated changes of naïve T cells remain poorly understood. Here we compared the transcriptome and chromatin accessibility in mature CD4 and CD8 thymocytes and in naïve CD4 and CD8 T cells of spleen between young (6-8 weeks) and old (79-121 weeks) C57Bl/6 mice. We used Agilent microarray method and identified the age-related altering gene expressions 1) only in mature CD4 and CD8 T cell from thymus, 2) shared by both thymus and spleen naïve T cells, and 3) only in naïve T cells from spleen. The shared changes include increased chemokine and chemokine receptor expressions and decreased cell cycle regulator expression. We further analyzed the chromatin basis of altered gene expression using Assaying Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) between young and old mice. We have identified age-related changes of chromatin accessibility in T cells from thymus and spleen, and some correlated changes between gene expression and chromatin accessibility. Overall, we observedmore age-related alterations of gene expression and chromatin accessibility inthymus than in spleen, suggesting some age-related changes of T cells in thymus did not retain in periphery. Together, our findings have identified tissue specific altered gene expressions and chromatin status in T cells during aging and further study of these altered genes will shed new insights into the mechanisms underlying these age-related changes.
2021-03-19 | GSE112391 | GEO
Project description:Aging of immune system is characterized by progressive decline of physiological and cellular function of T cells. Recent studies of naïve T cells from young and old mice have identified age-related altered gene expressions but the mechanisms underlying age associated changes of naïve T cells remain poorly understood. Here we compared the transcriptome and chromatin accessibility in mature CD4 and CD8 thymocytes and in naïve CD4 and CD8 T cells of spleen between young (6-8 weeks) and old (79-121 weeks) C57Bl/6 mice. We used Agilent microarray method and identified the age-related altering gene expressions 1) only in mature CD4 and CD8 T cell from thymus, 2) shared by both thymus and spleen naïve T cells, and 3) only in naïve T cells from spleen. The shared changes include increased chemokine and chemokine receptor expressions and decreased cell cycle regulator expression. We further analyzed the chromatin basis of altered gene expression using Assaying Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) between young and old mice. We have identified age-related changes of chromatin accessibility in T cells from thymus and spleen, and some correlated changes between gene expression and chromatin accessibility. Overall, we observedmore age-related alterations of gene expression and chromatin accessibility inthymus than in spleen, suggesting some age-related changes of T cells in thymus did not retain in periphery. Together, our findings have identified tissue specific altered gene expressions and chromatin status in T cells during aging and further study of these altered genes will shed new insights into the mechanisms underlying these age-related changes.
2021-03-19 | GSE112390 | GEO
Project description:Identification of age-related changes in gene expression and chromatin accessibility in T cells from thymus to periphery
| PRJNA445870 | ENA
Project description:Identification of age-related changes in gene expression and chromatin accessibility in T cells from thymus to periphery (44K)
| PRJNA445874 | ENA
Project description:To investigate the gene regulatory mechanisms driving T cell development, we generated single-cell transcriptomics and chromatin accessibility data from a human fetal thymus sample at 10 weeks of gestation.
2021-11-30 | E-MTAB-9828 | biostudies-arrayexpress
Project description:To investigate the gene regulatory mechanisms driving T cell development, we generated single-cell transcriptomics and chromatin accessibility data from a human fetal thymus sample at 10 weeks of gestation.
2021-11-30 | E-MTAB-9840 | biostudies-arrayexpress
Project description:The mechanism of egress of mature regulatory T cells (Tregs) from the thymus to the periphery remains enigmatic, as does the nature of those factors expressed in the thymic environment. Here, we examined the fate of thymic Tregs in TNFα/RelA double-knockout (TA-KO) mice, because TA-KO mice retain a Treg population in the thymus but have only a small Treg population at the periphery. Transplantation of whole TA-KO thymus to under the kidney capsule of Rag1 null mice failed to induce the production of donor-derived splenic Tregs expressing neuropilin-1 (Nrp1), which was reported to be a marker of naturally occurring Tregs, indicating that TA-KO thymic Tregs either do not leave the thymus or are lost at the periphery. We next transplanted enriched TA-KO thymic Tregs to the peripheries of TA-KO mice and traced mouse survival. Transplantation of TA-KO thymic Tregs rescued the lethality in TA-KO mice, demonstrating that TA-KO thymic Tregs remain functional at the periphery. The TA-KO thymic Treg population had highly demethylated CpG motifs in the foxp3 locus, indicating that the cells were arrested at a late-mature stage. Also, the population included a large subpopulation of Tregs expressing IL-7Rα, which is a possible marker of late-mature Tregs. Finally, TA-KO fetal liver chimeric mice developed an Nrp1+ splenic Treg population from TA-KO cells, suggesting that Treg arrest is caused by a lack of RelA in the thymic environment. Together, these results suggest that egress of mature Tregs from the thymus depends on RelA in the thymic environment. For the isolation of thymic Tregs, CD4+CD8α-CD25hi thymocytes were isolated from five 1.5- to 2-week-old TNFα-KO or TA-KO mice by using a FACSAria cell sorter. For the isolation of thymic stromal cells, 10 thymi from 1.5- to 2-week-old TNFα-KO or TA-KO mice were minced with scissors and treated with RPMI 1640 supplemented with 2% FCS, 0.2 mg/ml collagenase (Roche, Basel, Switzerland), 0.2 mg/ml dispase I (Roche), and 100 U/ml DNase I (Life Technologies) for 30 min with stirring. Digested thymi were centrifuged in a Percoll (GE Healthcare Bio-Sciences, Piscataway, NJ, USA) gradient (density, 1.115, 1.065, and PBS) at 1400g for 30 min. Cells in the upper layer were collected, and the CD45-EpCAM+ (thymic epithelial cells) and CD45+EpCAM- populations (enriched thymic stromal cells containing macrophages or dendritic cells) were sorted.
2015-03-04 | E-GEOD-64191 | biostudies-arrayexpress
Project description:Development of Foxp3-expressing regulatory T-lymphocytes (Treg) in the thymus is controlled by signals delivered in T-cell precursors via the TCR, co-stimulatory receptors, and cytokine receptors. In absence of IL-2, IL-15 or their receptors, fewer Treg apparently develop in the thymus. However, it was recently shown that a substantial part of thymic Treg are cells that had recirculated from the periphery back to the thymus, troubling interpretation of these results. We therefore reassessed the involvement of IL-2 and IL-15 in the development of Treg, taking into account Treg-recirculation. In three-week-old mice, when substantial amounts of recirculating Treg are present in the thymus, we found similarly reduced proportions of newly developed Treg in absence of IL-2 or IL-15, and in absence of both cytokines even less Treg developed. In neonates, when practically no recirculating Treg were found in the thymus, the absence of IL-2 led to substantially more reduced Treg-development than deficiency in IL-15. IL-2 and IL-15 differentially modulated the CD25, GITR, OX40, and CD73-phenotypes of thymus-egress-competent and periphery-seeding Treg. Interestingly, IL-2 and IL-15 also modulated the TCR-repertoire expressed by developing Treg. Upon transfer into Treg-less Foxp3sf mice, thymus-exit-competent Treg from IL-2- (and to a lesser extent IL-15-) deficient mice suppressed immunopathology less efficiently than wt Treg. Taken together, our results firmly establish important non-redundant quantitative and qualitative roles for IL-2 and, to a lesser extent, IL-15 in intrathymic Treg-development.
2022-08-29 | GSE153484 | GEO
Project description:The mechanism of egress of mature regulatory T cells (Tregs) from the thymus to the periphery remains enigmatic, as does the nature of those factors expressed in the thymic environment. Here, we examined the fate of thymic Tregs in TNFα/RelA double-knockout (TA-KO) mice, because TA-KO mice retain a Treg population in the thymus but have only a small Treg population at the periphery. Transplantation of whole TA-KO thymus to under the kidney capsule of Rag1 null mice failed to induce the production of donor-derived splenic Tregs expressing neuropilin-1 (Nrp1), which was reported to be a marker of naturally occurring Tregs, indicating that TA-KO thymic Tregs either do not leave the thymus or are lost at the periphery. We next transplanted enriched TA-KO thymic Tregs to the peripheries of TA-KO mice and traced mouse survival. Transplantation of TA-KO thymic Tregs rescued the lethality in TA-KO mice, demonstrating that TA-KO thymic Tregs remain functional at the periphery. The TA-KO thymic Treg population had highly demethylated CpG motifs in the foxp3 locus, indicating that the cells were arrested at a late-mature stage. Also, the population included a large subpopulation of Tregs expressing IL-7Rα, which is a possible marker of late-mature Tregs. Finally, TA-KO fetal liver chimeric mice developed an Nrp1+ splenic Treg population from TA-KO cells, suggesting that Treg arrest is caused by a lack of RelA in the thymic environment. Together, these results suggest that egress of mature Tregs from the thymus depends on RelA in the thymic environment.
2015-03-04 | GSE64191 | GEO
Project description:Thymus is the important immune organ, responsible for T cell development and differentiation.We conduct rhesus monkey thymus proteomics of FNC.
2024-08-10 | PXD050624 | Pride