Recently there has been growing interest in the immunomodulatory effects of endogenous danger signals known as alarmins. In this study, we explore a new combination therapy of anti-CD4 depleting antibody with an alarmin, high mobility group nucleosome binding protein 1 (HMGN1). Extremely low dose of HMGN1 with anti-CD4 depleting antibody exerted robust anti-tumor effects in Colon26 subtaneous murine model. To understand transcriptomic differences of CD8+ T cells in the tumor-bearing mice after treated with anti-CD4 depleting antibody or combination therapy of HMGN1 with anti-CD4 depleting antibody, we performed CD8 T cell transcriptome analysis using 3'SAGE-seq and Ion Proton sequencer. Overall design: CD8+ T cells were purified from single cell suspension of each implanted mouse tumor by lineage sorting (CD45-CD11b-B220-CD49b-Ter119-CD4-CD8+) through FACSAria. CD8 T cell transcriptome analysis were generated by 3'SAGE-seq using Ion Proton sequencer.
Combined treatment with HMGN1 and anti-CD4 depleting antibody reverses T cell exhaustion and exerts robust anti-tumor effects in mice.
Specimen part, Cell line, Subject
View SamplesLoss or reduction in function of tumor suppressor genes contributes to tumorigenesis. We identified a novel homozygous deletion of DACH1 in gliomas.
Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells.
Specimen part, Cell line
View SamplesTranscriptome analysis of post-mortem brain tissue specimens from three brain regions (BRs), entorinal, temporal and frontal cortices, of 71 Japanese brain-donor subjects to identify genes relevant to the expansion of neurofibrillary tangles. In total, 213 brain tissue specimens (= 71 subjects 3 BRs) were involved in this study. The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with the cognitive severity of Alzheimers disease (AD). To identify genes relevant to NFT expansion defined by the Braak stage, we conducted exon array analysis with an exploratory sample set consisting of 213 human post-mortem brain tissue specimens from the entorinal, temporal and frontal cortices of 71 brain-donor subjects: Braak NFT stages 0 (N = 13), III (N = 20), IIIIV (N = 19) and VVI (N = 19). We identified eight genes, RELN, PTGS2, MYO5C, TRIL, DCHS2, GRB14, NPAS4 and PHYHD1, associated with the Braak stage. The expression levels of three genes, PHYHD1, MYO5C and GRB14, exhibited reproducible association on real-time quantitative PCR analysis. In another sample set, including control subjects (N = 30) and patients with late-onset AD (N = 37), dementia with Lewy bodies (N = 17) and Parkinson disease (N = 36), the expression levels of two genes, PHYHD1 and MYO5C, were obviously associated with late-onset AD. Proteinprotein interaction network analysis with a public database revealed that PHYHD1 interacts with MYO5C via POT1, and PHYHD1 directly interacts with amyloid beta-peptide 42. It is thus likely that functional failure of PHYHD1 and MYO5C could lead to AD development.
Genes associated with the progression of neurofibrillary tangles in Alzheimer's disease.
Sex, Specimen part, Subject
View SamplesColon cancers typically contain tumor cell populations with differential WNT signaling activity. Colon cancer cells with high WNT-activity have been attributed increase tumorigenic potential and stem cell characteristics.
Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling.
Specimen part, Cell line
View SamplesStem cell-derived tissues have wide potential for modelling developmental and pathological processes as well as cell-based therapy. However, it has proven difficult to generate several key cell types in vitro, including skeletal muscle. In vertebrates, skeletal muscles derive during embryogenesis from the presomitic mesoderm (PSM). Using PSM development as a guide to establish conditions for the differentiation of monolayer cultures of embryonic stem (ES) cells into PSM-like cells without the introduction of transgenes or cell sorting.
A Gradient of Glycolytic Activity Coordinates FGF and Wnt Signaling during Elongation of the Body Axis in Amniote Embryos.
Specimen part, Disease, Cell line, Treatment, Time
View SamplesInfliximab (IFX) has been reported as the further therapy in intravenous immunoglobulin G (IVIG)-resistant Kawasaki disease (KD) patients. IFX is a monoclonal antibody that blocks the pro-inflammatory cytokine tumor necrosis factor (TNF)-, but how IFX affect KD vasculitis is unknown. We investigated expression profiling of whole blood cells to elucidate the molecular mechanisms of the effectiveness of IFX therapy and to find characteristic biomarker and an important target in refractory KD. Methods: Refractory KD patients who failed to respond to repeated intravenous immunoglobulin G (IVIG) infusions had received a single infusion of IFX as third therapy. To validate specifically transcripts abundance for IFX therapy, we detected the altered transcripts expression and signaling pathways of whole blood mRNA in these IFX-responsive patients (n=8) using Affymetrix array, comparing initial IVIG-responsive patients (n=6).Results: A total of 1,388 transcripts abundance were significantly altered before and after IFX treatment. These transcripts abundance in IFX had Nucleotide-binding oligomerization domain pathway that play a role in activation of NFB and IL-1 signaling pathway outside the field of TNF- signaling pathway. Fifty transcripts including Peptidase inhibitor-3 (PI3), Matrix metalloproteinase-8 (MMP8), Chemokine (C-C motif) receptor-2 (CCR2) and Pentraxin-3 (PTX3) were significantly down-regulated in IFX. Conclusion: We demonstrated that the inhibition of TNF- by IFX have affected various molecular mechanism materially for IVIG-resistant KD patients.
Transcriptional regulation by infliximab therapy in Kawasaki disease patients with immunoglobulin resistance.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesClinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone.
Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone.
Specimen part, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Restriction of intestinal stem cell expansion and the regenerative response by YAP.
Specimen part, Treatment
View SamplesRSpondin1 adenovirus was administered to mice and intestine was isolated for expression analysis 1 week later.
Restriction of intestinal stem cell expansion and the regenerative response by YAP.
Specimen part, Treatment
View SamplesThe rd1 mouse retina is a well-studied model of retinal degeneration where rod photoreceptors undergo cell death beginning at postnatal day P10 until P21. This period coincides with photoreceptor terminal differentiation in a normal retina. We have used the rd1 retina as a model to investigate early molecular defects in developing rod photoreceptors prior to the onset of degeneration. Using a microarray approach, we performed gene profiling comparing rd1 and wild type retinas at four time points starting at P2, prior to any obvious biochemical or morphological differences, and concluding at P8, prior to the initiation of cell death. We have identified genes that are differentially regulated in the rd1 retina at early time points, which may give insights into developmental defects that precede photoreceptor cell death. This is the first report of PRA1 expression in the retina. Our data support the hypothesis that PRA1 plays an important role in vesicular trafficking between the Golgi and cilia in differentiating and mature rod photoreceptors.
A role for prenylated rab acceptor 1 in vertebrate photoreceptor development.
Specimen part
View Samples