MED23, a subunit of the Mediator coactivator complex, is important for the expression of a subset of MAPK/ERK pathway-dependent target genes; however, the genes in this subset varies between cell types. MAPK/ERK pathway-dependent processes are essential for T-cell development and function, but whether MED23 has a role in this context is unknown. We generated Med23 conditional knockout mice and induced Med23 deletion in early T cell development using the lineage specific Lck-Cre transgene. While the total cell number and distribution of cell populations in the thymuses of Med23flox/flox;Lck-Cre mice were essentially normal, MED23 null T-cells failed to efficiently populate the peripheral lymphoid organs. MED23 null thymocytes displayed decreased expression of the MAPK/ERK-responsive genes Egr1, Egr2, as well as of the membrane glycoprotein Cd52 (CAMPATH-1). MED23 null CD4 single-positive thymocytes also showed decreased expression of KLF2 (LKLF), a T cell master regulatory transcription factor. Indeed, similarities between the phenotypes of mice lacking MED23 or KLF2 in T-cells suggest that KLF2 deficiency in MED23 null T-cells is one of their key defects. Mechanistic experiments using MED23 null MEFs further suggest that MED23 is required for full activity of the MAPK-responsive transcription factor MEF2, which has previously been shown to mediate Klf2 expression. In summary, our data indicate that MED23 has critical roles in enabling T-cells to populate the peripheral lymphoid organs, possibly by potentiating MEF2-dependent expression of the T-cell transcription factor KLF2.
T-cells null for the MED23 subunit of mediator express decreased levels of KLF2 and inefficiently populate the peripheral lymphoid organs.
Sex, Specimen part
View SamplesWe report that extended exposure to broad-spectrum terahertz radiation results in specific changes in cellular functions that are closely related to DNA-directed gene transcription. Our gene chip survey of gene expression shows that whereas 89% of the protein coding genes in mouse stem cells do not respond to the applied teraherz radiation, certain genes are activated, while other are repressed. RT-PCR experiments with selected gene probes corresponding to transcripts in the three groups of genes detail the gene specific effect. The response was not only gene specific but also irradiation conditions dependent. Our findings suggest that the applied terahertz irradiation accelerates cell differentiation toward adipose phenotype by activating the transcription factor peroxisome proliferator-activated receptor gamma (PPARG). Finally, our molecular dynamics computer simulations indicate that the local breathing dynamics of the PPARG promoter DNA coincides with the gene specific response to the THz radiation. We propose that THz radiation is a potential tool for cellular reprogramming.
Mammalian stem cells reprogramming in response to terahertz radiation.
Specimen part, Treatment
View SamplesTranscriptome analysis revealed that GDF15 and TGF-ß stimulation displayed similar expression patterns in differentially expressed genes. Overall design: GDF15 or TGF-ß stimulated NIH3T3 fibroblasts transcriptomes were analyzed by RNA-sequencing.
Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation.
No sample metadata fields
View SamplesLactic acid bacteria confer a variety of health benefits. Here we investigate the mechanisms by which Lactobacillus brevis KB290 enhances cell-mediated cytotoxic activity. We fed a diet containing KB290 (3 10^9 colony-forming units/g) , or potato starch, to 9-week-old female BALB/c mice for 1, 4, 7, or 14 days and examined the cytotoxic activity of splenocytes was measured. RNA was extracted from the spleen and analyzed for gene expression by DNA microarray.
Effect of Lactobacillus brevis KB290 on the cell-mediated cytotoxic activity of mouse splenocytes: a DNA microarray analysis.
Sex, Age, Specimen part
View SamplesPersistent colonization of the gastric mucosa by Helicobacter pylori (Hp) elicits chronic inflammation and aberrant epithelial cell proliferation, which increases the risk of gastric cancer. We examined the ability of microRNAs to modulate gastric cell proliferation in response to persistent Hp infection and found that epigenetic silencing of miR-210 plays a key role in gastric disease progression. Importantly, DNA methylation of the miR-210 gene was increased in Hp-positive human gastric biopsies as compared to Hp-negative controls. Moreover silencing of miR-210 in gastric epithelial cells promoted proliferation. We identified STMN1 and DIMT1 as miR-210 target genes and demonstrated that inhibition of miR-210 expression augmented cell proliferation by activating STMN1 and DIMT1. Together, our results highlight inflammation-induced epigenetic silencing of miR-210 as a mechanism of induction of chronic gastric diseases, including cancer, during Hp infection.
Epigenetic silencing of miR-210 increases the proliferation of gastric epithelium during chronic Helicobacter pylori infection.
Cell line
View SamplesDespite the importance of memory B cells for protection from recurrent infection, how these cells are selected during germinal center (GC) reactions remains unclear. We show here that light zone (LZ) GC B cells with lower affinity BCRs express a less CD40 signature and relatively high levels of Bach2, being prone to enter the memory B cell pool. We also find that Bach2 contributes to memory B cell generation in a Blimp-1 independent manner and that its higher expression confers on LZ GC cells a more advantage for entering the memory B cell compartment. Thus, our data support an instructive model in which weak T cell help keeps Bach2 expression relatively high, thereby being predisposed to enter the memory pool. Overall design: mRNA expression profiles of NP specific high and low affinity IgG1 LZ GC B cells were generated by deep sequencing using Illumina HiSeq 1500
Regulated selection of germinal-center cells into the memory B cell compartment.
Specimen part, Cell line, Subject
View SamplesDespite the importance of memory B cells for protection from recurrent infection, how these cells are selected during germinal center (GC) reactions remains unclear. We show here that light zone (LZ) GC B cells with lower affinity BCRs express a less CD40 signature and relatively high levels of Bach2, being prone to enter the memory B cell pool. We also find that Bach2 contributes to memory B cell generation in a Blimp-1-independent manner and that its higher expression confers on LZ GC cells a more advantage for entering the memory B cell compartment. Thus, our data support an instructive model in which weak T cell help keep Bach2 expression relatively high, thereby being predisposed to enter the memory pool. Overall design: mRNA expression profiles of Bach2-tdRFP low and high expression NP-specific IgG1 light zone GC B cells were generated by deep sequencing using Illumina HiSeq 1500.
Regulated selection of germinal-center cells into the memory B cell compartment.
Specimen part, Subject
View SamplesiPSC-derived NSPCs, which were induced by two different protocols (Embryoid body or Neural rosette) followed by expansion in free-floating culture (neurospheres), had closely resembled profiles.
Pathological classification of human iPSC-derived neural stem/progenitor cells towards safety assessment of transplantation therapy for CNS diseases.
Sex, Race
View SamplesThe entire small intestine was obseved by balloon endoscopy. Biopsy specimens were taken from jejunum, ileum and colon, respectively.
Reduced Human α-defensin 6 in Noninflamed Jejunal Tissue of Patients with Crohn's Disease.
Specimen part, Disease, Disease stage
View SamplesWe have previously established an in vitro tissue culture system (named VISUAL; Kondo et al., 2016), in which xylem and phloem differentiation can be induced with Arabidopsis thaliana cotyledons
BES1 and BZR1 Redundantly Promote Phloem and Xylem Differentiation.
Specimen part, Treatment, Time
View Samples