Atopic dermatitis and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. We show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of atopic dermatitis-specific Th2 and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in atopic dermatitis, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17. Furthermore, subcutaneous injection of recombinant TWEAK into naïve mice induces cutaneous inflammation with histological and molecular signs of both diseases. TWEAK is therefore a critical contributor to skin inflammation and a possible therapeutic target in atopic dermatitis and psoriasis. Overall design: Eight- to 12-week old male mice were used. TWEAK-deficient animals were bred in house on the C57BL/6 background, and Fn14-deficient animals on a BALB/c. Atopic Dermatitis-like disease was induced by epicutaneous treatment with HDM extract (10 µg/mouse and treatment) and SEB (500 ng/mouse and treatment) given in 2 cycles on days 1 and 4, and 14 and 17, on the shaved and tape-stripped back skin over a 23 day period.
TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis.
Treatment, Subject
View SamplesTumors consist of heterogeneous cell population, containing cancer cell subpopulations with anticancer drug-resistant property, called “persister” cells. To reveal the character of the persister cells, we analyzed gene expression profile of patient-derived gastric cells and residual cancer cells after treatment with 5-FU or SN38, an active metabolite of irinotecan. In our study, we identified ALDH1A3 as a marker and a cell proliferation factor of persister cells. To examine molecular pathways regulated by ALDH1A3, we analyzed gene expression profile of patient-derived gastric JSC15-3 in which ALDH1A3 was knocked down by using shRNAs.
ALDH1A3-mTOR axis as a therapeutic target for anticancer drug-tolerant persister cells in gastric cancer.
Specimen part, Cell line, Treatment
View SamplesHOX genes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. They also behave as oncogenes in some malignancies. In this study, we found high expression of the HOXD9 gene transcript in glioma cell lines and human glioma tissues by quantitative real-time PCR. Using immunocytochemistry, we observed HOXD9 protein expression in human brain tumor tissues, including astrocytomas and glioblastomas. To investigate the role of HOXD9 in gliomas, we silenced its expression in the glioma cell line U87 using HOXD9-specific siRNA, and observed decreased cell proliferation, cell cycle arrest, and induction of apoptosis. It was suggested that HOXD9 contributes to both cell proliferation and/or cell survival. The HOXD9 gene was highly expressed in a side population (SP) of SK-MG-1 cells that was previously identified as an enriched-cell fraction of glioma cancer stem-like cells. HOXD9 siRNA treatment of SK-MG-1 SP cells resulted in reduced cell proliferation. Finally, we cultured human glioma cancer stem cells (GCSCs) from patient specimens found with high expression of HOXD9 in GCSCs compared with normal astrocyte cells and neural stem/progenitor cells (NSPCs). Our results suggest that HOXD9 may be a novel marker of GCSCs and cell proliferation and/or survival factor in gliomas and glioma cancer stem-like cells, and a potential therapeutic target.
Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells.
Cell line
View SamplesTo identify the “time-lapse” TF networks during B lineage commitment, we established multipotent progenitors harboring a tamoxifen-inducible form of Id3, an in vitro system where virtually all cells became B cells within 6 days by simply withdrawing 4-OHT. In this study, transcriptome analysis at multiple time points was performed using the culture system. Overall design: Time-course transcriptomic profiles of multipotent iLS cells toward B committed cells were analyzed by deep sequencing, basically in triplicate, using Illumina Hiseq platform.
Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells.
Specimen part, Cell line, Subject, Time
View SamplesDuring cerebellar development, the main portion of the cerebellar plate neuroepithelium (NE) gives birth to Purkinje cells and interneurons, while the germinal zone at its dorsal edge, called the rhombic lip (RL), generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components work together to generate the intricate structure of the cerebellar anlage. In this study, we found that a polarized cerebellar anlage structure self-organizes in three-dimensional (3D) human ES cell (hESC) culture. This NE is capable of differentiating into electrophysiologically functional Purkinje cells. The addition of FGF19 promotes spontaneous generation of dorsoventrally polarized NE structures containing cerebellar and basal plates. Furthermore, further addition of SDF1 promoted the generation of stratified cerebellar plate NE with RL-like germinal zones self-forming at the edge. Thus, hESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellar anlage at the first trimester. Overall design: Examination of mRNA profile in two different treated human ES cells .
Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.
No sample metadata fields
View SamplesTo assess the role of two redox-sensitive transcriptional regulators, RoxSR and ANR, in Pseudomonas aeruginosa under aerobic conditions, microarray analysis was performed. Transcriptome profiles of roxSR mutant and anr mutant aerobically grown in LB medium were determined by Affymetrix GeneChip at both the exponential phase and early stationary phase and compared to that of the wild type strain.
Differential expression of multiple terminal oxidases for aerobic respiration in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesA unique embryonic stem cells showing nave state was established from primplantation mouse blastocyst but maintaind their self renew under FGF2 stimulus condition
Development of FGF2-dependent pluripotent stem cells showing naive state characteristics from murine preimplantation inner cell mass.
Specimen part, Cell line
View SamplesThe purpose of this study is to characterize gene expression changes that occur when conditional knock-out of Srf rescues mutant phenotypes in the cornea of Dstncorn1 mice.
Serum response factor: positive and negative regulation of an epithelial gene expression network in the destrin mutant cornea.
Specimen part
View SamplesD-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is a necessary enzyme for de novo L-serine biosynthesis via the phosphorylated pathway. We demonstrated previously that Phgdh is expressed exclusively by neuroepithelium and radial glia in developing mouse brain and later mainly by astrocytes. Mutations in the human PHGDH gene cause serine deficiency disorders (SDD) associated with severe neurological symptoms such as congenital microcephaly, psychomotor retardation, and intractable seizures. We recently demonstrated that genetically engineered mice, in which the gene for Phgdh has been disrupted, have significantly decreased levels of serine and glycine, and exhibit malformation of brain such as microcephaly. The Phgdh null (KO) embryos exhibit lethal phenotype after gestational day 14, indicating that the phosphorylated pathway is essential for embryogenesis, especially for brain development. It is worth noting that the Phgdh knockout (KO) embryos primarily displayed microcephaly, which is the most conspicuous phenotype of patients with SDD. Thus, Phgdh KO mice are a useful animal model for studying the effect of diminished L-serine levels on development of the central nervous system and other organs. To better understand the mechanism underlying the molecular pathogenesis of SDD, we sought to examine whether gene expression is altered in the Phgdh KO mouse model. We identify genes that have altered expression in the head of the Phgdh KO embryos using the GeneChip array. Some of the genes identified by this method belong in functional categories that are relevant to the biochemical and morphological aberrations of the Phgdh deletion.
Inactivation of the 3-phosphoglycerate dehydrogenase gene in mice: changes in gene expression and associated regulatory networks resulting from serine deficiency.
Specimen part
View SamplesHuR-deficient cells showed the decreased expression of genes involved in chemotaxis, cell proliferation and signal transduction.
Hu Antigen R Regulates Antiviral Innate Immune Responses through the Stabilization of mRNA for Polo-like Kinase 2.
Specimen part, Cell line
View Samples