Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA301052 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2927245.fastq.gz | Fastqsanger.gz | |||
| SRR2927246.fastq.gz | Fastqsanger.gz | |||
| SRR2927247.fastq.gz | Fastqsanger.gz | |||
| SRR2927248.fastq.gz | Fastqsanger.gz |
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Project description:Essential functions of the transcription factors TCF1 and SOX13 in gdT cell development (Sox13tg_Sox13lo)
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Project description:Innate-like gd T effector subsets are exported from the thymus as “memory-like” cells prewired for rapid, specialized function. Previously, we showed that emergent gd subsets distinguished by TCRg and TCRd usage in the fetal and adult thymus possess distinct global transcriptomes and the subset-specific combinatorial expression of High Mobility Group box transcription factors (HMG TFs) shown as a primary determinant of gd effector differentiation. While the detailed mechanism of HMG TFs cooperativity and counter-regulations are not fully understood, a key feature for IL-17 producing gd T effectors (Tgd17) is predicted to be context-dependent interactions between SOX13 and TCF1 that result in diversified target gene regulation. More SOX13 allow more TCF1 dockings on DNA. TCF1 chromatin occupancy in the Tgd17 gene cluster (V2 set) mimics when the amount of SOX13 is enhanced like the Sox13 transgenic system. Globally 75% of SOX13 binding is overlapped with TCF1 binding and V2 set-specifically 85% of SOX13 targets are overlapped with TCF1 targets. Mostly V2 sets are H3K4me3 (79%) and the genome wide analysis between TCF1 and SOX13 indicate cooperative and active SOX13-dependent-TCF1-modulations on V2 sets.
2018-11-01 | GSE74649 | GEO
Project description:Innate-like gd T effector subsets are exported from the thymus as “memory-like” cells prewired for rapid, specialized function. Previously, we showed that emergent gd subsets distinguished by TCRg and TCRd usage in the fetal and adult thymus possess distinct global transcriptomes and the subset-specific combinatorial expression of High Mobility Group box transcription factors (HMG TFs) shown as a primary determinant of gd effector differentiation. While the detailed mechanism of HMG TFs cooperativity and counter-regulations are not fully understood, a key feature for IL-17 producing gd T effectors (Tgd17) is predicted to be context-dependent interactions between SOX13 and TCF1 that result in diversified target gene regulation. More SOX13 allow more TCF1 dockings on DNA. TCF1 chromatin occupancy in the Tgd17 gene cluster (V2 set) mimics when the amount of SOX13 is enhanced like the Sox13 transgenic system. Globally 75% of SOX13 binding is overlapped with TCF1 binding and V2 set-specifically 85% of SOX13 targets are overlapped with TCF1 targets. The genome-wide analysis between TCF1 and SOX13 indicates cooperative and active SOX13-dependent-TCF1-modulations on V2 sets.
2018-11-01 | GSE74645 | GEO
Project description:Innate-like gd T effector subsets are exported from the thymus as “memory-like” cells prewired for rapid, specialized function. Previously, we showed that emergent gd subsets distinguished by TCRg and TCRd usage in the fetal and adult thymus possess distinct global transcriptomes and the subset-specific combinatorial expression of High Mobility Group box transcription factors (HMG TFs) shown as a primary determinant of gd effector differentiation. While the detailed mechanism of HMG TFs cooperativity and counter-regulations are not fully understood, a key feature for IL-17 producing gd T effectors (Tgd17) is predicted to be context-dependent interactions between SOX13 and TCF1 that result in diversified target gene regulation. More SOX13 allow more TCF1 dockings on DNA. TCF1 chromatin occupancy in the Tgd17 gene cluster (V2 set) mimics when the amount of SOX13 is enhanced like the Sox13 transgenic system. Globally 75% of SOX13 binding is overlapped with TCF1 binding and V2 set-specifically 85% of SOX13 targets are overlapped with TCF1 targets. The genome-wide analysis between TCF1 and SOX13 indicates cooperative and active SOX13-dependent-TCF1-modulations on V2 sets.
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Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
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Project description:Gamma delta T (gdT) cells with distinct properties develop in the embryonic and adult thymus and have been identified as critical players in a broad range of infections, antitumor surveillance, autoimmune diseases and tissue homeostasis. Despite their potential value for immunotherapy, differentiation of gdT cells in the thymus is incompletely understood. Here, we establish a high-resolution map of gdT cell differentiation from the fetal and adult thymus using single-cell RNA-sequencing. We reveal novel sub-types of immature and mature gdT cells and identify an unpolarized thymic population which is expanded in the blood and lymph nodes. Our detailed comparative analysis reveals remarkable similarities between the gene networks active during fetal and adult gdT cell differentiation. By performing a combined single-cell analysis of Sox13, Maf and Rorc knockout mice, we demonstrate sequential activation of these factors during IL-17-producing gdT cell (gdT17) differentiation. These findings substantially expand our understanding of gdT cell ontogeny in fetal and adult life. Our experimental and computational strategy provides a blueprint for comparing immune cell differentiation across developmental stages.
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2020-05-26 | PXD018764 | Pride
Project description:ab and gd T cells originate from a common, multi-potential precursor population in the thymus, but the molecular mechanisms regulating this lineage fate decision process are unknown. We have identified Sox13 as a gd-specific gene in the immune system. Using Sox13 transgenic mice, we show that SOX13 promotes gd T cell development while opposing ab T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gd T cells, but not ab T cells. One mechanism of SOX13 function is the inhibition of WNT/TCF signaling, suggesting that differential WNT/TCF activity is an essential parameter for this binary cell fate choice. Experiment Overall Design: CD4+CD8+ double positive thymocyte subsets were sorted by FACS using total pooled thymocytes from minimum of two mice and immediately lysed in Trizol. Comparison groups in each experiment were DP thymocytes from Sox13 transgenic mice and wild type B6 littermate controls. Gene expression profiling was performed according to the manufacturerâ??s protocol (Affymetrix). Labeled cRNA (from total RNA) was generated and applied to Affymetrix Mu11K(A and B) (expt 1) or muU74Av2 (expt 2) microarrays. Results were analyzed using Microarray Analysis Software v4 and v5 (Affymetrix).
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