Cellular differentiation is regulated through activation and repression of defined transcription factors. A hallmark of differentiation is a pronounced change in cell shape, which is determined by dynamics of the actin cytoskeleton. In de-differentiated fat (DFAT) cells and 3T3-L1 cells, we showed that treatment with the ROCK inhibitor Y-27632, by inducing remodeling of the actin cytoskelton, causes adipocyte differentiation. In addition, we found that depletion of MKL1, an actin binding transcriptional coactivator, elicits adipogenesis.
Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation.
Specimen part
View SamplesBranching morphogenesis in lung development is regulate by growth factor signaling. Wnt signaling is one of the important singnaling pathway that is required for progenitor maintainance. In the presence of CHIR99021, an agonist for the beta-catenin pathway of Wnt signaling, specific group of genes are upregulated in cultured lung epithelium.
Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition.
Specimen part
View SamplesDifferential gene expression profiles of neurospheres derived from different regions of the adult brain.
Environmental impact on direct neuronal reprogramming in vivo in the adult brain.
Specimen part
View SamplesTo understand molecular mechanisms underlying the growth inhibitory ativity of Stearoyl-CoA desaturase-1 (SCD1) inhibitor, we performed microarray analysis using HCT-116 colorectal cancer cells, in which SCD1 was pharmacologically blocked or genetically ablated.
Feedback activation of AMPK-mediated autophagy acceleration is a key resistance mechanism against SCD1 inhibitor-induced cell growth inhibition.
Specimen part, Cell line, Treatment
View SamplesTo explore TNF-related genes in GPI-induced arthritis, we performed GeneChip analysis using arthritic splenocytes and control-immunized splenocytes. Among the arrayed TNFalpha-related genes, TIARP mRNA was highly expressed in arthritic splenocytes, with levels exceeding more than 20-times the control splenocytes
Tumor necrosis factor alpha-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis.
Sex, Specimen part
View SamplesMouse skin bitten by Zika virus-infected mosquitoes were isolated and performed RNA-seq Overall design: Examination of host responses after Zika virus-infected mosquito bites, in duplicate
Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice.
Specimen part, Cell line, Treatment, Subject
View SamplesHuman Tregs isolated from PBMCs were cultured in the absence or presence of IL-12 (20ng/ml) for four days and were performed mRNA-seq. Overall design: mRNA profiles of human Treg stimulated with IL-12 (Th1 condition)
Activated β-catenin in Foxp3<sup>+</sup> regulatory T cells links inflammatory environments to autoimmunity.
Age, Subject
View SamplesActing downstream of many growth factors, extracellular signal-regulated kinase (ERK) plays a pivotal role in regulating cell proliferation and tumorigenesis, where its spatiotemporal dynamics, as well as its strength, determine cellular responses. Here, we uncover the ERK activity dynamics in intestinal epithelial cells (IECs) and their association with tumour characteristics. In vivo imaging identified two distinct modes of ERK activity, sustained and pulse-like activity, in IECs. The sustained and pulse-like activity depended on ErbB2 and EGFR, respectively. Notably, deregulated activation of Wnt signalling, the earliest event in intestinal tumorigenesis, augmented EGFR signalling and exalted it to a dominant driver of ERK activity dynamics, which rendered IECs addicted to EGFR signalling. Furthermore, the frequency of ERK activity pulses was also increased to promote cell proliferation. Thus, ERK activity dynamics are defined by composite inputs from EGFR and ErbB2 signalling in IECs and their alterations underlie tumour-specific sensitivity to pharmacological EGFR inhibition. In this microarray analysis, we aimed to elucidate molecular mechanisms that mediate Wnt signalling activation-induced alterations in EGFR-ERK signalling dynamics.
Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine.
Specimen part
View SamplesObjective: Adult Stills disease (ASD) is a systemic disorder of unknown etiology characterized by high spiking fever, rash and arthritis. The purpose of this study was to determine the pathogenic roles of specific genes in ASD. Methods: Differentially expressed genes (DEGs) were examined by DNA microarray and validated by quantitative PCR using monocytes isolated from patients with active-ASD, inactive-ASD and healthy controls. The correlation between validated DEGs and ASD activity was analyzed. After inflammasome activation with LPS and Nigericin, the production of IL-1, IL-18, inflammasome and autophagy related proteins in DEGs-overexpressing THP-1 cells was carried out by ELISA or western blotting. DEGs-overexpressing THP-1 cells were treated with an inhibitor of autophagy followed by assessment of IL-1 and IL-18 production by ELISA and western blotting method.Conclusions: The overexpression of PLAC8 in monocytes might play a regulatory role in the production of IL-1 and IL-18 by the enhancement of autophagy, resulting in the suppression of ASD. Results:A total of 68 genes were highly expressed in monocytes isolated from active-ASD patients, relative to their expression in inactive-ASD patients and healthy controls. After validation of expression of 13 genes (CLU, FCGR1B, PLAC8, TLR1, S100A12, CD55, PIM1, BCL2A1, SOD2, PLSCR1, CYP1B1, STEAP4, IL1RN), the expression of PLAC8 was significantly higher in active-ASD patients than the other groups. In ASD, PLAC8 expression level correlated with serum levels of CRP, ferritin and IL-18. Stimulation of monocytes with lipopolysaccharide resulted in PLAC8 upregulation. LPS or Nigericin stimulation of PLAC8-overexpressing THP-1, but not THP-1 cells< was associated with significant decrease in IL-1 and IL-18 production. PLAC8 overexpressing in THP-1 cells was associated with enhanced autophagy and suppression of IL-1 and IL-18 production. Conclusions: PLAC8 upregulation in monocytes seemed to play a regulatory role in the production of IL-1 and IL-18 through enhanced autophagy, resulting in suppression of ASD. The results highlight the role of PLAC8 in the pathogenesis of ASD and suggest its potential suitability as a therapeutic target in ASD.
Placenta Specific 8 Suppresses IL-18 Production through Regulation of Autophagy and Is Associated with Adult Still Disease.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesMED1/TRAP220, a subunit of the transcriptional Mediator/TRAP complex, is crucial for various biological events through its interaction with distinct activators such as nuclear receptors and GATA family activators. In hematopoiesis, MED1 plays a pivotal role in optimal nuclear receptor-mediated myelomonopoiesis and GATA-1-induced erythropoiesis. In this study, we present evidence that MED1 in stromal cells is involved in supporting hematopoietic stem and/or progenitor cells (HSPCs) through osteopontin (OPN) expression. We found that the proliferation of bone marrow (BM) cells cocultured with MED1 knockout (Med1-/-) mouse embryonic fibroblasts (MEFs) was significantly suppressed when compared to the control. Furthermore, the number of long-term culture-initiating cells (LTC-ICs) was attenuated for BM cells cocultured with Med1-/- MEFs. The vitamin D receptor (VDR)- and Runx2-mediated expression of OPN, as well as Mediator recruitment to the Opn promoter, was specifically attenuated in the Med1-/- MEFs. Addition of OPN to these MEFs restored the growth of cocultured BM cells and the number of LTC-ICs, both of which were attenuated by the addition of the anti-OPN antibody to Med1+/+ MEFs and to BM stromal cells. Consequently, MED1 in niche appears to play an important role in supporting HSPCs, by upregulating VDR- and Runx2-mediated transcription on the Opn promoter.
The transcriptional mediator subunit MED1/TRAP220 in stromal cells is involved in hematopoietic stem/progenitor cell support through osteopontin expression.
Specimen part
View Samples