Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part due to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to easily assess tumor samples for degree of anaplasia. Instead, identification of genetic signatures able to distinguish among anaplastic grades and thus predict high versus low risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia would also yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes are also able to accurately predict severe anaplasia in our dataset. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high-risk retinoblastoma.
Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma.
Specimen partView Samples
Soybean plants that do not produce a sink, such as depodded or male sterile plants, exhibit physiological and morphological changes during the reproductive stages, including increased levels of nitrogen and starch in the leaves and a delayed senescence. To identify transcriptional changes that occur in leaves of sink-limited plants, we used RNAseq to compare gene expression levels in trifoliate leaves from depodded and ms6 male sterile plants and control plants. In sink-limited tissues, we observed a deferral of the expression of senescence-associated genes and a continued high expression of genes associated with the maturity phase of leaf development. We identified GO-terms associated with growth and development and storage protein in sink limited tissues. We also identified that the bHLH. ARFs, and SBP transcription factors were expressed in sink limited tissues while the senescing control leaves expressed WRKY and NAC transcription factors. We identified genes that were not expressed during normal leaf development but highly expressed in sink-limited plants, including the D4 “non-yellowing” gene. These changes highlighted several metabolic pathways that were involved in distinct modes of resource parttioning in the “stay green” leaves. Overall design: Timecourse gene expression analysis of sink-limited soybean leaves. Gene expression was profiled from R2 growth stage (flowering) until the onset of leaf seenscence, and contrasted between mechanically and genetically sink-limited soybeans.
Transcriptional profiling of mechanically and genetically sink-limited soybeans.
Specimen part, Subject, TimeView Samples
We use RNA sequencing technology in a time course study to measure transcript abundance from three developmental stages in cotyledons and five stages in the trifoliate leaf of Glycine max to identify genes with distinct temporal patterns of expression during leaf or cotyledon development. We also examine the diffrences between these two photosynthetic tissues. Overall design: Timecourse Expression analysis of Cotyledon Development and Leaf Development using RNAseq on distinct timepoints. 3 stages of the cotyledon were sequenced with 3 biological replicates in each stage. Five stages of the leaf were sequenced with 3 biological replicates for each stage.
Developmental profiling of gene expression in soybean trifoliate leaves and cotyledons.
Specimen part, SubjectView Samples
Transcriptome analyses using a wild-type strain of Saccharomyces cerevisiae were performed to assess the overall pattern of gene expression during the transition from glucose-based fermentative to glycerol-based respiratory growth. These experiments revealed a complex suite of metabolic and structural changes associated with the adaptation process. Alterations in gene expression leading to remodeling of various membrane transport systems and the cortical actin cytoskeleton were observed. Transition to respiratory growth was accompanied by alterations in transcript patterns demonstrating not only a general stress response, as seen in earlier studies, but also the oxidative and osmotic stress responses. In some contrast to earlier studies, these experiments identified modulation of expression for many genes specifying transcription factors during the transition to glycerol-based growth. Importantly and unexpectedly, an ordered series of changes was seen in transcript levels from genes encoding components of the TFIID, SAGA (Spt-Ada-Gcn5-Acetyltransferase), and SLIK (Saga LIKe) complexes and all three RNA polymerases, suggesting a modulation of structure for the basal transcriptional machinery during adaptation to respiratory growth. In concert with data given in earlier studies, the results presented here highlight important aspects of metabolic and other adaptations to respiratory growth in yeast that are common to utilization of multiple carbon sources. Importantly, they also identify aspects specific to adaptation of this organism to growth on glycerol as sole carbon source.
Transcriptome profiling of Saccharomyces cerevisiae during a transition from fermentative to glycerol-based respiratory growth reveals extensive metabolic and structural remodeling.
No sample metadata fieldsView Samples
Rsf1p is a putative transcription factor required for efficient growth using glycerol as sole carbon source but not for growth on the alternative respiratory carbon source ethanol.
Rsf1p is required for an efficient metabolic shift from fermentative to glycerol-based respiratory growth in S. cerevisiae.
No sample metadata fieldsView Samples
Studied gene regulation in bronchial smooth muscle cells following vitamin D stimulation.
1alpha,25-dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells induces autocrine, contractility, and remodeling processes.
Sex, Age, Specimen part, RaceView Samples
A putative yeast mitochondrial upstream activating sequence (UAS) was used in a one-hybrid screening procedure that identified the YJR127C ORF on chromosome X. This gene was previously designated ZMS1 and is listed as a transcription factor on the SGD website. Real time RT-PCR assays showed that expression of YJR127C/ZMS1 was glucose-repressible, and a deletion mutant for the gene showed a growth defect on glycerol-based but not on glucose- or ethanol-based medium. Real time RT-PCR analyses identified severely attenuated transcript levels from GUT1 and GUT2 to be the source of that growth defect, the products of GUT1 and GUT2 are required for glycerol utilization. mRNA levels from a large group of mitochondria- and respiration-related nuclear genes also were shown to be attenuated in the deletion mutant. Importantly, transcript levels from the mitochondrial OLI1 gene, which has an associated organellar UAS, were attenuated in the DeltaYJR127C mutant during glycerol-based growth, but those from COX3 (OXI2), which lacks an associated mitochondrial UAS, were not. Transcriptome analysis of the glycerol-grown deletion mutant showed that genes in several metabolic and other categories are affected by loss of this gene product, including protein transport, signal transduction, and others. Thus, the product of YJR127C/ZMS1 is involved in transcriptional control for genes in both cellular genetic compartments, many of which specify products required for glycerol-based growth, respiration, and other functions.
The YJR127C/ZMS1 gene product is involved in glycerol-based respiratory growth of the yeast Saccharomyces cerevisiae.
No sample metadata fieldsView Samples
Mammalian gonadal sex determination is dependent on proper expression of sex determining genes in fetal gonadal somatic support cells (i.e., pre-granulosa and pre-Sertoli cells in XX and XY gonads, resp.). We used a unique transgenic mouse strain combined with microarray profiling to identify all the differentially expressed transcripts in XX and XY isolated somatic support cells during critical stages of gonadal development and differentiation.
New candidate genes identified for controlling mouse gonadal sex determination and the early stages of granulosa and Sertoli cell differentiation.
Sex, Specimen partView Samples
Microarray expression profiling was used to identify genes expressed misexpressed in wild-type Arabidopsis seedlings treated with 5-aza-2 deoxyctidine (5AC) or trichostatin A (TSA), and in decrease in dna methylation1 (ddm1) mutant seedlings.
Changes in global gene expression in response to chemical and genetic perturbation of chromatin structure.
Specimen partView Samples
Dynamic interaction between prostate cancer and the bone microenvironment is a major contributor to metastasis of prostate cancer to bone. In this study we utilized an in-vitro co-culture model of PC3 prostate cancer cells and osteoblasts followed by microarray based gene expression profiling to identify previously unrecognized prostate cancer-bone microenvironment interactions. Factors secreted by PC3 cells resulted in the up-regulation of many genes in osteoblasts associated with bone metabolism and cancer metastasis, including Mmp13, Il-6 and Tgfb2, and down-regulation of Wnt inhibitor Sost. To determine whether altered Sost expression in the bone microenvironment has an effect on prostate cancer metastasis, we co-cultured PC3 cells with Sost knockout (SostKO) osteoblasts and wildtype (WT) osteoblasts and identified several genes differentially regulated between PC3-SostKO osteoblast co-cultures and PC3-WT osteoblast co-cultures. Co-culturing PC3 cells with WT osteoblasts up-regulated cancer-associated long noncoding RNA (lncRNA) MALAT1 in PC3 cells. MALAT1 expression was further enhanced when PC3 cells were co-cultured with SostKO osteoblasts and treatment with recombinant Sost down-regulated MALAT1 expression in these cells. Our results suggest that reduced Sost expression in the tumor microenvironment may promote bone metastasis by up-regulating MALAT1 in prostate cancer.
Cancer-Osteoblast Interaction Reduces Sost Expression in Osteoblasts and Up-Regulates lncRNA MALAT1 in Prostate Cancer.
Cell lineView Samples