Background: Glucocorticoids (GCs) are widely used anti-inflammatory drugs. While useful in clinical practice, patients taking GCs often suffer from skeletal side effects including growth retardation and decreased bone quality in adults. On a physiological level, GCs have been implicated in the regulation of chondrogenesis and osteoblast differentiation, as well as maintaining homeostasis in cartilage and bone. We identified the glucocorticoid receptor (GR) as a potential regulator of chondrocyte hypertrophy in a microarray screen of primary limb bud mesenchyme micromass cultures. Some targets of GC regulation in chondrogenesis are known, but the global effects of pharmacological GC doses on chondrocyte gene expression have not been comprehensively evaluated.
Expression profiling of Dexamethasone-treated primary chondrocytes identifies targets of glucocorticoid signalling in endochondral bone development.
No sample metadata fields
View SamplesGlucocorticoids are used for the treatment of inflammatory conditions but they also cause many side-effects.
Glucocorticoids induce gastroparesis in mice through depletion of l-arginine.
Treatment, Time
View SamplesAnalysis of bone marrow derived macrophages (BMDM) incubated with dexamethasone&IL4 (Dexa+IL4), B16F1 tumor conditioned medium (cmB16), and B16F1 tumor conditioned medium supplemented with dexamethasone&IL4 (cmB16+dexa+IL4). Results allow detection of genes that require synergistic stimulation of tumor factors and Th2 cytokines.
Synergistic activation by p38MAPK and glucocorticoid signaling mediates induction of M2-like tumor-associated macrophages expressing the novel CD20 homolog MS4A8A.
Specimen part
View SamplesTumor-associated macrophages (TAMs) represent alternatively activated (M2) macrophages that support tumor growth. Previously, we have described a special LYVE-1(+) M2 TAM subset in vitro and in vivo; gene profiling of this TAM subset identified MS4A8A as a novel TAM molecule expressed in vivo by TAM in mammary carcinoma and malignant melanoma. In vitro, Ms4a8a mRNA and MS4A8A protein expression was strongly induced in bone marrow-derived macrophages (BMDMs) by combining M2 mediators (IL-4, glucocorticoids) and tumor-conditioned media (TCM). Admixture of MS4A8A(+) TCM/IL-4/GC-treated BMDM significantly enhanced the tumor growth rate of subcutaneously transplanted TS/A mammary carcinomas. Upon forced overexpression of MS4A8A, Raw 264.7 macrophage-like cells displayed a special gene signature. Admixture of these MS4A8A(+) Raw 264.7 cells also significantly enhanced the tumor growth rate of subcutaneously transplanted mammary carcinomas. To identify the signaling pathways involved in synergistic induction of MS4A8A, the major signaling cascades with known functions in TAM were analyzed. Although inhibitors of NF-B activation and of the MAPK JNK and ERK did not show relevant effects, the p38/ MAPK inhibitor SB203580 strongly and highly significantly (p > 0.001) inhibited MS4A8A expression on mRNA and protein level. In addition, MS4A8A expression was restricted in M2 BMDM from mice with defective GC receptor (GR) dimerization indicating that classical GR gene regulation is mandatory for MS4A8A induction. In conclusion, expression of MS4A8A within the complex signal integration during macrophage immune responses may act to fine tune gene regulation. Furthermore, MS4A8A(+) TAM may serve as a novel cellular target for selective cancer therapy.
Synergistic activation by p38MAPK and glucocorticoid signaling mediates induction of M2-like tumor-associated macrophages expressing the novel CD20 homolog MS4A8A.
Specimen part
View SamplesBoth bone morphogenetic proteins (BMPs) and histone deacetylases (HDACs) have previously been established to play a role in the development of the three major cell types of the central nervous system: neurons, astrocytes, and oligodendrocytes. We have previously established a connection between these two protein families, showing that HDACs suppress BMP-promoted astrogliogenesis in the embryonic striatum. Since HDACs act in the nucleus to effect changes in transcription, an unbiased analysis of their transcriptional targets could shed light on their downstream effects on BMP-signaling. Using neurospheres from the embryonic striatum as an in vitro system to analyze this phenomenon, we have performed microarray expression profiling on BMP2- and trichostatin A (TSA)-treated cultures, followed by validation of the findings with quantitative RT-PCR and protein analysis.
Distinct and overlapping gene regulatory networks in BMP- and HDAC-controlled cell fate determination in the embryonic forebrain.
Specimen part, Treatment
View SamplesFoxp1/4 transcription factors are conserved transcriptional repressors expressed in overlapping patterns during lung development as well as in the adult lung. However, the role of Foxp1/4 in development and homeostasis of the pseudostratified epithelium of the proximal airways and trachea is unknown.
Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2.
Specimen part
View SamplesIdentification of TBF1-dependent and SA, elf18-responsive genes in Arabidopsis
The HSF-like transcription factor TBF1 is a major molecular switch for plant growth-to-defense transition.
Specimen part, Treatment
View SamplesThe ZFP36L3 protein is a rodent-specific, placenta- and yolk sac-specific member of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins. These proteins bind to AU-rich elements in target mRNAs, and promote their deadenylation and decay. Mice deficient in ZFP36L3 exhibited decreased neonatal survival rates, but no apparent morphological changes in the placenta or surviving offspring. Zfp36l3 is paternally imprinted, with profound parent-of-origin effects on gene expression. RNASeq of KO placental mRNA revealed many significantly affected transcripts, some of which exhibited decreased decay rates in differentiated trophoblast stem cells derived from KO blastocysts. The type 1 transferrin receptor mRNA was unexpectedly decreased in KO placentas, despite an increase in its stability. This receptor is critical for placental iron uptake from the maternal circulation, and its decrease was accompanied by decreased iron stores in the KO fetus, suggesting that this intrauterine deficiency might have deleterious consequences in later life. Overall design: Examination of gene expression differences in yolk sac tissue between wild-type and knockout mice groups with 4 biological replicates in each group
Deficiency of the placenta- and yolk sac-specific tristetraprolin family member ZFP36L3 identifies likely mRNA targets and an unexpected link to placental iron metabolism.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation.
Specimen part, Disease, Cell line, Treatment
View SamplesArid3a, a transcription factor known for its requirement in B-lymphocyte development, has been recently identified as a member of ES cell pluripotency network. Arid3a is moderately expressed in ES cells, and its expression is gradually increased during differentiation. Since Arid3a shows the highest expression in placenta, we hypothesized that Arid3a may play important roles in TE development. We report that Arid3a is a central regulator of both TE-specific and pluripotency-associated gene expression during ES cell differentiation. While dispensable for self-renewal, we observed that knockdown of Arid3a delays differentiation of ES cells. Induction of Arid3a leads ES cells to promote differentiation, specifically towards TE lineage. Moreover, these Arid3a-overexpressing cells maintained in TE culture media are sufficient to generate functional trophoblast stem-like cells, suggesting roles of Arid3a in TE differentiation. By integrative analyses using the chromosomal targets of Arid3a with expression profiling, we revealed the dual roles of Arid3a, as a direct activator of TE-specific genes and a repressor of pluripotency-associated genes. We further revealed the repressive roles of Arid3a are mediated by histone deacetylases (HDACs). Taken together, our results demonstrate that Arid3a is a critical novel regulator in TE lineage specification.
Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation.
Disease, Cell line, Treatment
View Samples