The transcription factor BATF is required for Th17 and TFH differentiation. Here, we show that BATF also has a fundamental role in regulating effector CD8+ T cell differentiation. BATF-deficient CD8+ T cells show profound defects in effector expansion and undergo proliferative and metabolic catastrophe early after antigen encounter. BATF, together with IRF4 and Jun proteins, binds to and promotes early expression of genes encoding lineage-specific transcription-factors (T-bet and Blimp-1) and cytokine receptors, while paradoxically repressing genes encoding effector molecules (IFNg and granzyme B). Thus, BATF amplifies TCR-dependent transcription factor expression and augments inflammatory signal propagation but restrains effector gene expression. This checkpoint prevents irreversible commitment to an effector fate until a critical threshold of downstream transcriptional activity has been achieved.
The transcription factor BATF operates as an essential differentiation checkpoint in early effector CD8+ T cells.
No sample metadata fields
View SamplesThe onset of the liver inflamentation in the Sox17+/- embryos.
Sox17 haploinsufficiency results in perinatal biliary atresia and hepatitis in C57BL/6 background mice.
Specimen part
View SamplesHeat shock protein 90 (Hsp90) is essential for the stability and the function of many client proteins, such as ERB2, C-RAF, CDK4, HIF-1 aplha and AKT. Recent reports demonstrated that inhibition of Hsp90 modulates multiple functions required for survival of human cancer, such as myeloma (Mitsiades et al, Blood:107, 1092, 2006), The aim of this study is evaluate the effect of Hsp90 inhibition, and to identify molecular pathways responsible for anti-proliferative effect on ATL cells. For Hsp90 inhibition, Geldanamycin derivates, 17AAG (17-allylamino -17-demethoxygeldanamycin) and 17DMAG (17-(dimethylaminoethylamino) 17-demethoxygeldanamycin) were used in this study. Interleukin 2-independent ATL cell lines (MT-2 and MT-4) and an interleukin 2-dependent ATL cell line (TaY-E10) were incubated, with or without Hsp90 inhibitors.
Anti-proliferative activity of heat shock protein (Hsp) 90 inhibitors via beta-catenin/TCF7L2 pathway in adult T cell leukemia cells.
No sample metadata fields
View SamplesAdult T-cell leukemia (ATL) is a fatal neoplasia derived from HTLV-1 infected T lymphocytes exhibiting constitutive activation of NF-kB. To elucidate the complex molecular mechanism of anti-tumor effect of the proteasome inhibitor, bortezomib in ATL cells, we attempted to perform gene expression profiling.
Induction of heme oxygenase-1 by cobalt protoporphyrin enhances the antitumour effect of bortezomib in adult T-cell leukaemia cells.
No sample metadata fields
View SamplesInnate lymphoid cells (ILCs) comprise three groups of recently identified tissue resident immune cell lineages that play critical roles in protective immune responses and tissue homeostasis. While significant progress has been made in defining the key protein mediators of ILC development and function, how cis-acting epigenetic regulatory elements or long non-coding RNAs (lncRNAs) regulate ILCs is unknown. Herein, we describe a cis-regulatory element demarcated by a novel lncRNA that controls the maturation, function and lineage identity of group 1 ILCs while being dispensable for early ILC development and homeostasis of mature ILC2s and ILC3s. We named this ILC1-restricted lncRNA Rroid. The Rroid locus controls the functional specification and lineage identity of ILC1 by promoting chromatin accessibility and STAT5 deposition at the promoter of its neighboring gene, Id2, in response to the ILC1-specific cytokine IL-15. Overall design: RNA-seq for gene expression in mouse NK cells
Group 1 Innate Lymphoid Cell Lineage Identity Is Determined by a cis-Regulatory Element Marked by a Long Non-coding RNA.
Specimen part, Subject
View SamplesOne of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates.
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part, Disease, Disease stage
View SamplesTranscription profiling of X.laevis development.
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part
View SamplesTranscription profiling of chicken development
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part
View SamplesTranscription profiling of mouse development
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sex, Specimen part, Disease, Disease stage
View SamplesBiopsies (lymph nodes, ascites or hydrothorax) from 60 patients with cancer of unknown primary origin were analyzed.
A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer.
Specimen part, Disease, Disease stage
View Samples