SOX13 regulated genes in CD4+CD8+ double positive thymocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE6311 | GEO | 2006/12/20
SECONDARY ACCESSION(S): PRJNA100519
REPOSITORIES: GEO
Similar Datasets
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).
2008-06-14 | E-GEOD-6311 | biostudies-arrayexpress
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 | GSE74641 | 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. 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:Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines were constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines were identified. The expression of SOX13/SCAF1 was manipulated in GC cell lines where relevant biological and molecular analyses were performed. Molecular docking and computational screening were performed to screen potential inhibitors of SOX13. We showed that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics, NADPH production and chemo- and immune-resistance. Zanamivir, reverted the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Overall, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.
2023-11-17 | GSE247870 | GEO
Project description:SOX13 was identified as a novel flow-sensitive transceiption factor. We found that siRNA-mediated knockdown of SOX13 increased endothelial inflammatory responses even under the unidirectional laminar shear stress (ULS, mimicking s-flow) condition. To understand the underlying mechanisms, we conducted an RNAseq study in HAECs treated with SOX13 siRNA under shear conditions (ULS vs. oscillatory shear mimicking d-flow). We found 94 downregulated and 40 upregulated genes that changed in a shear- and SOX13-dependent manner. Several cytokines, including CXCL10 and CCL5, were the most strongly upregulated genes in HAECs treated with SOX13 siRNA.
2022-09-27 | GSE207087 | GEO
Project description:a RNA transcriptome sequencing analysis was performed in SNU-668 erastin-resistant cells that were transfected with shRNA-SOX13 or control shRNA
2022-08-18 | GSE211072 | GEO
Project description:gd T cells are increasingly understood to play critical roles in host defense and can also contribute to immune mediated pathology; however, their origins remain poorly understood. There is growing evidence suggesting that immature bipotent progenitors in the thymus are instructed to adopt the ab and γδ fates, respectively, by differences in T cell receptor (TCR) signal strength or duration, with stronger and more prolonged signals directing adoption of the gd fate. These differences in TCR signaling instruct fate through graded induction of Id3, which in turn, produces graded reductions in the ability of E box DNA binding proteins (E proteins) to bind DNA. While E proteins play a central role in regulating lymphoid fate decisions, their downstream gene targets through which they specify fate have not been identified. Understanding how E proteins control gd lineage commitment requires a comprehensive, network-based approach. Consequently, we employed ChIP-Seq to identify the enhancers whose occupancy by E-proteins was altered by TCR signaling during gd lineage commitment and we identified their targets using a chromosome capture method termed Hi-C. These data were then integrated into a comprehensive, E-protein-focused, genome-wide network describing the genomic reorganization that occurs during gd lineage commitment. These studies revealed that E protein occupancy of enhancers was far more dramatically remodeled in progenitors adopting the gd lineage fate than in uncommitted progenitors exposed to the same selecting environment and has led to the identification of specific regulatory elements through which gd lineage commitment and effector function is controlled. One such element plays a critical role in controlling the expression of the transcription factor (TF) ThPOK, as well as the effector function of γδ T cells. Thus, our comprehensive approach has provided critical new insights into the molecular processes orchestrating gd lineage commitment and provides a framework for molecular dissection of both lineage commitment and effector function.
2021-03-10 | GSE162291 | GEO
Project description:gd T cells are increasingly understood to play critical roles in host defense and can also contribute to immune mediated pathology; however, their origins remain poorly understood. There is growing evidence suggesting that immature bipotent progenitors in the thymus are instructed to adopt the ab and γδ fates, respectively, by differences in T cell receptor (TCR) signal strength or duration, with stronger and more prolonged signals directing adoption of the gd fate. These differences in TCR signaling instruct fate through graded induction of Id3, which in turn, produces graded reductions in the ability of E box DNA binding proteins (E proteins) to bind DNA. While E proteins play a central role in regulating lymphoid fate decisions, their downstream gene targets through which they specify fate have not been identified. Understanding how E proteins control gd lineage commitment requires a comprehensive, network-based approach. Consequently, we employed ChIP-Seq to identify the enhancers whose occupancy by E-proteins was altered by TCR signaling during gd lineage commitment and we identified their targets using a chromosome capture method termed Hi-C. These data were then integrated into a comprehensive, E-protein-focused, genome-wide network describing the genomic reorganization that occurs during gd lineage commitment. These studies revealed that E protein occupancy of enhancers was far more dramatically remodeled in progenitors adopting the gd lineage fate than in uncommitted progenitors exposed to the same selecting environment and has led to the identification of specific regulatory elements through which gd lineage commitment and effector function is controlled. One such element plays a critical role in controlling the expression of the transcription factor (TF) ThPOK, as well as the effector function of γδ T cells. Thus, our comprehensive approach has provided critical new insights into the molecular processes orchestrating gd lineage commitment and provides a framework for molecular dissection of both lineage commitment and effector function.
2021-03-10 | GSE162290 | GEO
Project description:Background Wnt signaling is implicated in many developmental decisions, including stem cell control, as well as in cancer. There are relatively few target genes known of the Wnt pathway. Results We have identified target genes of Wnt signaling using microarray technology and human embryonal carcinoma cells stimulated with active Wnt protein. The ~50 genes upregulated early after Wnt addition include the previously known Wnt targets Cyclin D1, MYC, ID2 and beta TRCP. The newly identified targets, which include MSX1, MSX2, Nucleophosmin, Follistatin, TLE/Groucho, Ubc4/5E2, CBP/P300, Frizzled and REST/NRSF, have important implications for understanding the roles of Wnts in development and cancer. The protein synthesis inhibitor cycloheximide blocks induction by Wnt, consistent with a requirement for newly synthesized beta - catenin protein prior to target gene activation. The promoters of nearly all the target genes we identified have putative TCF binding sites; and we show that the TCF binding site is required for induction of Follistatin. Several of the target genes have a cooperative response to a combination of Wnt and BMP. Conclusion Wnt signaling activates genes that promote stem cell fate and inhibit cellular differentiation; and regulates a remarkable number of genes involved in its own signaling system.
2005-09-02 | E-SMDB-1827 | biostudies-arrayexpress