Polycomb group proteins (PcG) are well known by their function in the regulation of developmental processes. PcG mediated regulation of genetic programs required for proper development are triggered by EZH2 H3K27 methyltransferase activity. EZH1 can partially substitute EZH2 activity. However, unlike EZH2, EZH1 is presence in differentiated and adult tissues suggesting additional biological functions. Here we show that EZH2 is predominantly expressed in neural stem cells being essential for neural stem cells self renewal and homeostasis. There, it controls the transcriptional state of cell cycle regulators, such as CIP1. But it is also necessary to regulate genes involved in surveillance and neuroepithelial polarity. In contrast, EZH1 expression is more abundant in differentiated cells within the spinal cord and its downregulation unables neural stem cells to differentiate. All together our data reveal a complementary but non-redundant role of EZH2 and EZH1 in neurogenesis.
EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21.
Specimen part
View SamplesGene expression profiles in synovial biopsies from patients with rheumatoid arthritis (RA) display a high level of plasticity related to disease activity and response to therapy.
Higher expression of TNFα-induced genes in the synovium of patients with early rheumatoid arthritis correlates with disease activity, and predicts absence of response to first line therapy.
Sex, Age, Disease
View SamplesTNF antagonists are routinely used in severe rheumatoid arthritis (RA) patients who failed conventional DMARD therapy. According to large clinical trials, the three available drugs (adalimumab, infliximab and etanercept) display similar effects in terms of efficacy, tolerability and side effects. These studies also indicate that about 25% of RA patients treated with TNF-antagonists do not display any significant clinical improvement.
Gene expression profiling in the synovium identifies a predictive signature of absence of response to adalimumab therapy in rheumatoid arthritis.
Specimen part, Disease
View SamplesTNFalpha and IL1beta play a pathogenic role in rheumatoid arthritis. Both cytokines are known to activate cytokine and metalloproteinase secretion by synovial fibroblasts. In the present study, we wanted to investigate whether TNFalpha and IL1beta displayed differential effects on cultured Fibroblast-like Synovial Cells derived from RA patients. Global gene expression analyses indicated that both cytokines induced similar genes in these cells.
Gene expression profiling in the synovium identifies a predictive signature of absence of response to adalimumab therapy in rheumatoid arthritis.
Specimen part, Disease, Treatment
View SamplesStearoyl-CoA desaturase (SCD) is the rate-limiting enzyme catalyzing the conversion of saturated fatty acids palmitate and stearate to monounsaturated fatty acids palmitoleate and oleate. During adipocyte differentiation, SCD expression increases concomitantly with several transcription factors and lipogenic genes.
Inhibition of stearoyl-CoA desaturase-1 in differentiating 3T3-L1 preadipocytes upregulates elongase 6 and downregulates genes affecting triacylglycerol synthesis.
Specimen part, Treatment
View SamplesTCF-1 is an HMG family transcription factor which is known to be activated by the canonical Wnt signaling pathway and modulated by other signals such as those derived from T cell receptor. We found that during CD8 T cell responses, TCF-1 deficiency impaired long-term maintenance of antigen-specific memory CD8 T cells.
Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1.
Specimen part
View SamplesThe transcriptome of naive OT-I T cells was compared to memory CD8 T cells after 1, 2, 3, or 4 infection with ovalbumin expressing Listeria monocytogenes (LM-OVA).
Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation.
Specimen part
View SamplesMemory CD8+ P14 cells were generarted through adoptive transfer and infection with LCMV armstrong. Then, early memory (after 30 - 45 days) and late memory (after 8 months) cells were sort purified based on CD62L expression.
Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection.
Specimen part, Time
View SamplesComparison of the transcriptome between control Tfh and Tcf1 long isoform-deficient Tfh cells Overall design: SMARTA CD4+ T cells (control or Tcf1 long isoform deficient) were adoptively transferred into B6.SJL recipient mice and then infected with LCMV-Arm. On day 8 after infection, the splenocytes were isolated, and CD45.2+CD4+CXCR5+PD-1 negative cells were sorted as Tfh cells and used in RNAseq analysis.
Differential Requirements for Tcf1 Long Isoforms in CD8<sup>+</sup> and CD4<sup>+</sup> T Cell Responses to Acute Viral Infection.
Specimen part, Subject
View SamplesThe majority of babies in the US are formula-fed instead of breast fed. There are major differences in the composition of formulas and breast milk and yet little is known about metabolic differences in babies as the result of feeding these very different diets and how that might affect development or disease risk in later life. One concern is that soy-based formulas might have adverse health effects in babies as a result of the presence of low levels of estrogenic phytochemicals genistein and daidzein which are normally present in soy beans. In the current study, we used a piglet model to look at this question. Piglets were either fed breast milk from the sow or were fed two different infant formulas (cows milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food. Blood glucose and lipids were measured. Formula-fed pigs were found to have lower cholesterol than breast fed piglets and in addition had larger stores of iron in their liver.Microarray analysis was carried out to see if changes in liver gene expression could explain these effects of formula feeding. It was found that overall gene expression profiles were influenced by formula feeding compared to breast fed neonates. Gender-independent and unique effects of formula influenced cholesterol and iron metabolism. Further, soy formula feeding in comparison to milk-based formula failed to reveal any estrogenic actions on hepatic gene expression in either male or female pigs.
Formula feeding alters hepatic gene expression signature, iron and cholesterol homeostasis in the neonatal pig.
Sex
View Samples