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GSE33338
Homo sapiens
3 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression.
Sample Metadata Fields
Sex, Age, Cell line
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 44 Downloadable Samples
Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals. From 46 OOM samples, which are frequently discarded during routine corrective surgeries on patients with orofacial clefts, we derived mesenchymal stem cells and correlated the individual genetic variants with gene expression from these cultured cells. Through this strategy, we detected significant cis-eQTLs (i.e., DNA variants affecting gene expression) and selected a few candidates to conduct an association study in a large Brazilian cohort (624 patients and 668 controls). This resulted in the discovery of a novel susceptibility locus for NSCL/P, rs1063588, the best eQTL for the MRPL53 gene, where evidence for association was mostly driven by the Native American ancestry component of our Brazilian sample. MRPL53 (2p13.1) encodes a 39S protein subunit of mitochondrial ribosomes and interacts with MYC, a transcription factor required for normal facial morphogenesis. Our study illustrates not only the importance of sampling admixed populations but also the relevance of measuring the functional effects of genetic variants over gene expression to dissect the complexity of disease phenotypes.
Publication Title
MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Papillary thyroid cancers (PTC) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison to the central regions of primary PTCs, the invasive fronts overexpressed TGFbeta, NFkappaB and integrin pathway members, and regulators of small G-proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell-cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 35 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required for the development and maintenance of both a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is a common mechanism of PTC invasion and that vimentin regulates thyroid cancer EMT in vitro.
Publication Title
Gene expression and functional evidence of epithelial-to-mesenchymal transition in papillary thyroid carcinoma invasion.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 46 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study gut microbiota from young or old conventional mice was transferred to young germ-free mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyers patches, and mesenteric lymph nodes from conventionalized germ-free mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here we show by transferring aged microbiota to young germ-free mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the germ-free mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young germ-free mice.
Publication Title
Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To understand the molecular control of development and regeneration in the mammalian cochlear sensory epithelia, we performed a comparative study of gene expression patterns between postnatal day-3 (P3) and adult stages using a microarrays approach.
Publication Title
Transcriptomic analysis of the developing and adult mouse cochlear sensory epithelia.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 158 Downloadable Samples
IlluminaHiSeq2000
Description
Pineal function follows a 24-hour schedule, dedicated to the conversion of night and day into a hormonal signal, melatonin. In mammals, 24-hour changes in pineal activity are controlled by a neural pathway that includes the central circadian oscillator in the suprachiasmatic nucleus and the superior cervical ganglia (SCG), which innervate the pineal gland. In this study, we have generated the first next-generation RNA sequencing evidence of neural control of the daily changes in the pineal transcriptome. We found over 3000 pineal transcripts that are differentially expressed (p <0.001) on a night/day basis (70% of these genes increase at night, 376 with fold change >4 or <1/4), the majority of which had not been previously identified as such. Nearly all night/day differences were eliminated by neonatal removal or decentralization of the SCG, confirming the importance of neural input for differential night/day changes in transcript abundance. In contrast, very few non-rhythmic genes showed evidence of changes in expression due to the surgical procedure itself, which is consistent with the hypothesis that post neonatal neural stimulation is not required for cell fate determination and maintenance of phenotype. Many of the transcripts that exhibit marked differential night/day expression exhibited similar changes in response to in vitro treatment with norepinephrine, the SCG neurotransmitter which mediates pineal regulation. Similar changes were also seen following treatment with an analog of the norepinephrine second messenger, cyclic AMP. Overall design: For the in vivo data, there were 8 biological conditions: day and night time points for each of four surgical groups: Control (Ctrl) Sham-surgery (Sham), Decentralized (DCN), and Ganglionectomized (SCGX). Samples were pooled into three biological replicates for each biological condition. For the in vitro data there were 3 biological conditions: Untreated control (CN), DBcAMP-treated (DB), and Norepinephrine-treated (NE). For the pineal enrichment comparison, three samples (i.e. no biological replicates) were used: pineal-day, pineal-night and mixed-tissue. For the mixed tissues sample, the following tissues from three rats sacrificed at ZT7 were used: cortex, cerebellum, midbrain, hypothalamus, hindbrain, spinal cord, retina, pituitary, heart, liver, lung, kidney, skeletal muscle, small intestine, adrenal gland. Total RNA was extracted from each tissue, and then equal amounts of each of the 15 tissues were combined for the final pooled sample.
Publication Title
Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on the Rat Pineal Transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray analysis was performed to determine the transcriptional profiles of NKT, CD1d-aGC+ Va24-, and CD4 T cells.
Publication Title
A naive-like population of human CD1d-restricted T cells expressing intermediate levels of promyelocytic leukemia zinc finger.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 133 Downloadable Samples
- NextSeq 500
Description
The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune mediated inflammatory diseases (IMIDs). Yet, despite their key role in disease, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue driven pathologies observed in IMIDs such as inflammation and damage . Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of FAPa+ synovial cells suppressed both inflammation and bone erosions in murine models of resolving and persistent arthritis. Single cell transcriptional analysis identified two distinct fibroblast subsets: FAPa+ THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPa+ THY1- destructive fibroblasts restricted to the synovial lining. When adoptively transferred into the joint, FAPa+ THY1- fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation whereas transfer of FAPa+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell based therapies aimed at modulating inflammation and tissue damage. Overall design: Serum transfer inflammatory arthritis (STIA) was induced by intravenous injection of 100 µl of arthritogenic KRN serum into naive C57BL/6 mice. From these mice, CD45-ve live Podoplanin (PDPN)+ synovial cells from hind limb joints were sort purified at day 9 (n=3 biological replicates, each comprised of cells from the joints of three animals). Individuals subsets of CD45- PDPN+ cells were further sort puified in the following populations FAP?+ THY1- (n=10 mice); FAP?+ THY+ (n=13 mice); FAP?- THY1+ (n=7 mice) and FAP?- THY1- (n=5 mice). Small bulk RNA sequencing was performed on each of these cell populations with each sample representing a biological replicate comprising of cells isolated from the synovial joints of both hind limbs from a single mouse).
Publication Title
Distinct fibroblast subsets drive inflammation and damage in arthritis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The use of nucleic acids from formalin-fixed paraffin-embedded (FFPE) tissues for high-throughput molecular techniques, such as microarray gene expression profiling has become widespread in molecular research area. However, working with FFPE tissues is challenging because of degradation, cross-linking with proteins, and RNA chemical modifications. Also, there is no generally accepted procedure for RNA extraction to microarray analysis. Thus, there is a need for a standardized workflow for FFPE samples to study microarray transcriptome profiling. Therefore, the main purpose of this study was to conduct a standardized process from deparaffinization to RNA extraction and microarray gene expression analysis. Firstly, deparaffinization procedure was optimized for FFPE samples and then Trizol, PicoPure RNA isolation kit, and Qiagen RNeasy FFPE kit performances were compared in terms of yield and purity. Finally, two different cRNA/cDNA preparation and labeling protocols with two different array platforms (Affymetrix Human Genome U133 Plus 2.0 and U133_X3P) were also evaluated to determine which combination gives the best percentage of present call. Our optimization study shows that the Qiagen RNeasy FFPE kit with modified deparaffinization step gives better results (RNA quantity and quality) than the other two isolation kits. The Ribo-SPIA protocol and U133_X3P array combination gave a significantly higher percentage of present calls than the 3 IVT cDNA amplification and labeling system. However, no significant differences were found between the two array platforms. These results present a workflow for microarray gene expression profiling of FFPE tissues. The findings also indicate that sufficient quality gene expression data can be obtained from FFPE-derived RNA.
Publication Title
Optimization of gene expression microarray protocol for formalin-fixed paraffin-embedded tissues.
Sample Metadata Fields
Specimen part
View Samples