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At least 1,171 records · Page 65Linked to original sources
PubMed2005

The study of metabolic pathways in tumors based on the transcriptome.

DNA microarray technology revolutionized gene-expression analysis in molecular biology to observe patterns of gene expression in genomic scale. We review the biological aspects of genome-wide gene-expression activity in tumors specially focusing on the analysis of enzyme coding genes. First, the methods for analyzing gene-expression data for the study of metabolome in silico are discussed showing SV40T antigen expressing liver tumor data as an example. Next, an application for tumor metabolome analysis utilizing a reference set of gene-expression profiles is shown.

Animals↗
PubMed2006

Mining the oocyte transcriptome.

Mammalian folliculogenesis and oocyte physiology are complex and not fully understood. However, major advances over the past 15 years in our ability to create and study in vivo models have improved our understanding of these essential physiological processes. More recently, the availability of vast arrays of DNA sequence information in the forms of "complete" genomes, expressed sequence tag libraries and microarray data from reproductive tissues have stimulated the discovery of new information through genome scanning, prediction programs and in silico screening techniques. These technological improvements will help to expand our understanding of folliculogenesis and oocyte physiology and improve human reproductive health.

Bone Morphogenetic Protein 15↗
PubMed2026

Integrated single-cell and bulk transcriptomic analysis identifies a novel senescent fibroblast subtype associated with poor prognosis in acral melanoma.

BACKGROUND: Acral melanoma (AM) exhibits significant intratumoral heterogeneity, but its tumor microenvironment (TME) and immune regulation remain unclear. This study aims to dissect TME heterogeneity and establish a prognostic model based on key cell subpopulations. METHODS: We collected AM single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Unsupervised clustering, CellChat, and Scissor analysis were performed to characterize cellular heterogeneity, cell-cell communication, and prognosis-related cell subpopulations. Kaplan-Meier analysis was used to assess the prognostic value of key genes, which were further validated by multiplex immunohistochemistry (mIHC). RESULTS: In AM, Mel_C2, C7, and C9 with high SEMA6A and KIT expression were strongly linked to poor prognosis. We further identified a senescent fibroblast subpopulation (sCAF_CDKN2A) characterized by high fibroblast senescence signature (FSS) scores. Integrating Scissor analysis of fibroblast subtypes with bulk prognostic data, we identified COL3A1, VCAN, and KIT as prognosis-associated genes upregulated in poor-outcome-related fibroblast subsets. Cell-cell communication analysis revealed that sCAF_CDKN2A engages in an immunosuppressive network, interacting with regulatory T cells (Tregs) via MIF signaling and receiving signals from exhausted CD8+ T cells through PPIA-BSG interactions. Using transcription factor expression patterns from these fibroblast subtypes, we constructed a prognostic model that effectively stratified patients into distinct risk groups with significant differences in overall survival (OS). mIHC confirmed significantly higher protein levels of SEMA6A and COL3A1 in tumor tissues compared to matched normal tissues. CONCLUSIONS: We established a novel prognostic model for AM and identified sCAF_CDKN2A as an immunosuppressive senescent fibroblast subpopulation driving poor prognosis.

Acral melanoma↗
PubMed2004

Resistance and susceptibility to tuberculosis analysed at the transcriptome level: lessons from mouse macrophages.

Gene expression patterns associated with resistance and susceptibility to tuberculosis (TB) were investigated at the macrophage level in the well-defined mouse model of infection. Oligonucleotide microarrays were used to analyse the regulation of gene expression in murine bone marrow-derived macrophages infected with Mycobacterium tuberculosis. Four mouse strains, known to differ in terms of growth permissiveness for M. tuberculosis in infected tissues, in the development of pulmonary pathology, and in the rate of premature death due to tuberculosis, were compared: C57BL/6 and BALB/c representing resistant, DBA/2 and CBA/J representing susceptible mouse strains. Genes (55) were regulated more than two-fold in macrophages of all strains investigated following M. tuberculosis infection. Importantly, 18 genes were commonly regulated only in macrophages of the two resistant strains upon infection, and 102 genes were commonly regulated exclusively in macrophages of the two susceptible strains. Using this approach, we have therefore identified more than 100 genes potentially associated with resistance and susceptibility, respectively, to TB at the macrophage level. A tentative interpretation of our microarray data suggests that macrophages from susceptible mice predominantly stimulate the recruitment of cells that contribute disproportionately to tissue damage rather than to microbial elimination. In conclusion, microarray gene chips are useful tools for generating new hypotheses about resistance and susceptibility to TB, and the mouse model can now be used to subject candidate genes identified by this approach to further functional analyses.

Animals↗
PubMed2005

From transcriptome to immunome: identification of DTH inducing proteins from a Phlebotomus ariasi salivary gland cDNA library.

Delayed-type hypersensitivity (DTH) response to arthropod vector salivary proteins is associated with protection against pathogen transmission. Massive cDNA sequencing, high-throughput DNA plasmid construction and DNA immunisation were used to identify twelve DTH inducing proteins isolated from a Phlebotomus ariasi salivary gland cDNA library. Additionally, nine P. ariasi DNA plasmids produced specific anti-saliva antibodies, four of these showed a Th1 immune response while the other two exhibited a Th2 profile as determined by IgG2a and IgG1 isotype switching, respectively. In order to validate the specificity of sand fly DNA plasmids, mice previously exposed to sand fly saliva were intradermally injected once with selected P. ariasi plasmids and a specific DTH response consisting of infiltration of mononuclear cells in varying proportions was observed at 24 and 48 h. This approach can help to identify DTH inducing proteins that may be related to host protection against vector-borne diseases or other disease agents where cellular immune response is protective.

Amino Acid Sequence↗
PubMed2006

Angiogenic transcriptome of human microvascular endothelial cells: Effect of hypoxia, modulation by atorvastatin.

Hypoxia changes expression of angiogenic genes. Statins were also reported to affect blood vessel formation. However, data on the effects of statins on endothelial cells in hypoxia are limited. Here, effect of hypoxia and atorvastatin was assessed in human microvascular endothelial cells (HMEC-1). Hypoxia (1% O2) up-regulated vascular endothelial growth factor-A (VEGF-A) but, unexpectedly, it decreased interleukin-8 (IL-8) and placenta growth factor (PlGF) expression. Atorvastatin (0.1-1 microM) attenuated PlGF in HMEC-1 in normoxia while it decreased VEGF-A and IL-8 production both in normoxia and hypoxia. Notably, the expression of VEGF-D, macrophage scavenger receptor-1 (MSR1), transforming growth factor beta receptor III (TGFbetaR3) and inhibitor of DNA binding 3 (ID3) was augmented by atorvastatin in cells cultured in normoxia, while in hypoxia the statin attenuated their expression. These data showed that hypoxia influenced in the opposite way the expression of major endothelial genes, augmenting VEGF-A and decreasing IL-8 and PlGF. The influence of atorvastatin on angiogenic gene expression is complex, and final pro- or anti-angiogenic outcome of statin therapy remains to be established for numerous angiogenesis-related diseases.

Atorvastatin↗
PubMed2006

Effect of textile wastewaters on Saccharomyces cerevisiae using DNA microarray as a tool for genome-wide transcriptomics analysis.

Textile mill effluents (TMEs) discharged from the textile industry can be considered as one class of hypothetical toxicants in the environment. To investigate the potential toxicity of TMEs, we applied cDNA microarray technology to examine the genome-wide expression profiles in model eukaryote, Saccharomyces cerevisiae. The results revealed a rich source of genetic information for the yeast cells that were exposed to the untreated and treated TMEs. Among the 5956 valid genes, 275 genes were up-regulated and 40 genes were down-regulated for the untreated TMEs. On the other hand, only 90 genes were up-regulated, and 29 genes were down-regulated upon exposure to the treated TMEs. The changes in gene expression were also confirmed by RT-PCR. The potent up- and down-regulation of genes suggest that yeast cells undergo genome-wide changes in mRNA expression, indicative of a stress response. Additionally, a classification into specific functional gene categories indicated that untreated and even treated TMEs still had toxicity. Especially, the genes related to oxidative stress, such as AHP1, ATX1, GRX1, TRX1 and TRX2, were up-regulated in treated TMEs that can directly reach to surface and ground waters, and sediments.

Down-Regulation↗
PubMed2004

Comprehensive transcriptome analysis of differentiation of embryonic stem cells into midbrain and hindbrain neurons.

Neurogenesis is one of the most complex events in embryonic development. However, little information is available regarding the molecular events that occur during neurogenesis. To identify regulatory genes and underlying mechanisms involved in the differentiation of embryonic stem (ES) cells to neurons, gene expression profiling was performed using cDNA microarrays. In mouse ES cells, we compared the gene expression of each differentiated cell stage using a five-stage lineage selection method. Of 10,368 genes, 1633 (16%) known regulatory genes were differentially expressed at least 2-fold or greater at one or more stages. At stage 3, during which ES cells differentiate into neural stem cells, modulation of nearly 1000 genes was observed. Most of transcription factors (Otx2, Ebf-3, Ptx3, Sox4, 13, 18, engrailed, Irx2, Pax8, and Lim3), signaling molecules (Wnt, TGF, and Shh family members), and extracellular matrix/adhesion molecules (collagens, MAPs, and NCAM) were up-regulated. However, some genes which may play important roles in maintaining the pluripotency of ES cells (Kruppel-like factor 2, 4, 5, 9, myeloblast oncogene like2, ZFP 57, and Esg-1) were down-regulated. The many genes identified with this approach that are modulated during neurogenesis will facilitate studies of the mechanisms underlying ES cell differentiation, neural induction, and neurogenesis.

Animals↗
PubMed2004

Side population cells isolated from different tissues share transcriptome signatures and express tissue-specific markers.

Side Population (SP) cells, isolated from murine adult bone marrow (BM) based on the exclusion of the DNA dye Hoechst 33342, exhibit potent hematopoietic stem cell (HSC) activity when compared to Main Population (MP) cells. Furthermore, SP cells derived from murine skeletal muscle exhibit both hematopoietic and myogenic potential in vivo. The multipotential capacity of SP cells isolated from variable tissues is supported by an increasing number of studies. To investigate whether the SP phenotype is associated with a unique transcriptional profile, we characterized gene expression of SP cells isolated from two biologically distinct tissues, bone marrow and muscle. Comparison of SP cells with differentiated MP cells within a tissue revealed that SP cells are in an active transcriptional and translational status and underexpress genes reflecting tissue-specific functions. Direct comparison of gene expression of SP cells isolated from different tissues identified genes common to SP cells as well as genes specific to SP cells within a particular tissue and further define a muscle and bone marrow environment. This study reports gene expression of muscle SP cells, common features and differences between SP cells isolated from muscle and bone marrow, and further identifies common signaling pathways that might regulate SP cell functions.

Animals↗
PubMed2006

Temporal transcriptome of mouse ATDC5 chondroprogenitors differentiating under hypoxic conditions.

The formation of cartilage takes place in vivo in an environment of reduced oxygen tension. To study the effect of hypoxia on the process of chondrogenesis, ATDC5 mouse chondroprogenitor cells were induced to differentiate by the addition of insulin and cultured under ambient and hypoxic conditions corresponding to 21% and 1% O2 in the gas phase, respectively. The production of extracellular proteoglycans as well as the transcriptional profile of 104 selected genes was determined by real-time RT-PCR. Hypoxia alone induced early chondrogenesis as evidenced by the synthesis of glycosaminoglycans and expression of aggrecan and collagen type II genes. Surprisingly, however, hypoxic incubation of insulin-treated cells delayed and suppressed the insulin-mediated early chondrogenesis and almost completely blocked hypertrophic differentiation. Analysis of the gene expression yielded several clues as to the mechanisms involved. In addition, a group of genes was identified that have not previously been associated with hypoxia, including Ak4, Akt3, Col X, Fmod, Ier3, IGFbp4, MafF, Mxi1, Rcor2, Rras, Sox6, Tnni2, Wnt5a, and Zfp313.

Aggrecans↗
PubMed2004

Quantitative analysis of the cardiac fibroblast transcriptome-implications for NO/cGMP signaling.

Cardiac fibroblasts regulate tissue repair and remodeling in the heart. To quantify transcript levels in these cells we performed a comprehensive gene expression study using serial analysis of gene expression (SAGE). Among 110,169 sequenced tags we could identify 30,507 unique transcripts. A comparison of SAGE data from cardiac fibroblasts with data derived from total mouse heart revealed a number of fibroblast-specific genes. Cardiac fibroblasts expressed a specific collection of collagens, matrix proteins and metalloproteinases, growth factors, and components of signaling pathways. The NO/cGMP signaling pathway was represented by the mRNAs for alpha(1) and beta(1) subunits of guanylyl cyclase, cGMP-dependent protein kinase type I (cGK I), and, interestingly, the G-kinase-anchoring protein GKAP42. The expression of cGK I was verified by RT-PCR and Western blot. To establish a functional role for cGK I in cardiac fibroblasts we studied its effect on cell proliferation. Selective activation of cGK I with a cGMP analog inhibited the proliferation of serum-stimulated cardiac fibroblasts, which express cGK I, but not higher passage fibroblasts, which contain no detectable cGK I. Currently, our data suggest that cGK I mediates the inhibitory effects of the NO/cGMP pathway on cardiac fibroblast growth. Furthermore the SAGE library of transcripts expressed in cardiac fibroblasts provides a basis for future investigations into the pathological regulatory mechanisms underlying cardiac fibrosis.

Adaptor Proteins, Signal Transducing↗
PubMed2005

gNCA: a framework for determining transcription factor activity based on transcriptome: identifiability and numerical implementation.

Network Component Analysis (NCA) is a network structure-driven framework for deducing regulatory signal dynamics. In contrast to classical approaches such as principal component analysis or independent component analysis, NCA makes use of the connectivity structure from transcriptional regulatory networks to restrict the decomposition to a unique solution. However, the existing version of NCA cannot incorporate information beyond the network topology such as information obtained from regulatory gene knockouts that constrain the dynamics of regulatory signals. The ability of incorporating such information enables a more accurate and self-consistent analysis over different experiments and extends NCA to systems that may not satisfy the identifiability criteria of NCA. In this paper, we derive a generalized form of NCA, gNCA, which significantly expands the capability of transcription network analysis by incorporating regulatory signal constraints arising from genetic knockouts. The theoretical bases including criteria for uniqueness of solution and distinguishability between networks are derived. In addition, numerical techniques for robust decomposition are discussed. gNCA is then demonstrated using an Escherichia coli wild-type strain and an isogenic arcA deletion mutant during a carbon source transition.

Bacterial Outer Membrane Proteins↗
PubMed2002

Unmasking venom gland transcriptomes in reptile venoms.

While structural studies of reptile venom toxins can be achieved using lyophilized venom samples, until now the cloning of precursor cDNAs required sacrifice of the specimen for dissection of the venom glands. Here we describe a simple and rapid technique that unmasks venom protein mRNAs present in lyophilized venom samples. To illustrate the technique we have RT-PCR-amplified a range of venom protein transcripts from cDNA libraries derived from the venoms of a hemotoxic snake, the Chinese copperhead (Deinagkistrodon acutus), a neurotoxic snake, the black mamba (Dendroaspis polylepis), and a venomous lizard, the Gila monster (Heloderma suspectum). These include a metalloproteinase and phospholipase A2 from D. acutus, a potassium channel blocker, dendrotoxin K, from D. polylepis, and exendin-4 from H. suspectum. These findings imply that the apparent absence and/or lability of mRNA in complex biological matrices is not always real and paves the way for accelerated acquisition of molecular genetic data on venom toxins for scientific and potential therapeutic purposes without sacrifice of endangered herpetofauna.

Animals↗
PubMed2003

Ozone-induced disruptions of lung transcriptomes.

We have analyzed changes in approximately 4000 lung mRNAs, with GeneChips, in mice exposed to 1 ppm O(3) for three consecutive nights (8 h per night). Differential gene expression analysis identified approximately 260 O(3) sensitive genes; approximately 80% of these were repressed and approximately 20% were induced in O(3)-exposed mice compared to the air-exposed controls. A 20-fold induction of serum amyloid A3 mRNA by O(3) suggested activation of NF-kappaB and CCAAT/enhancer binding protein-mediated pathways by inflammatory cytokines. Induction (up to 14-fold) of 12 genes that increase DNA synthesis and cell cycle progression, and increase (approximately 7-fold) in CD44 mRNA and macrophage metalloelastase suggested a state of O(3)-induced hyperplasia and lung remodeling. Several mRNAs encoding enzymes of xenobiotic metabolism and cytoskeletal functions were repressed and may suggest cytokine mediated suppression of cytochrome P450 expression and cachexia-like inflammatory state in ozone-exposed lungs. The expressions of approximately 30 genes of immune response were also repressed. Collectively this genome-wide analysis of lungs identified ozone-induced disruption of gene transcriptional profile indicative of increased cellular proliferation under suppressed immune surveillance and xenobiotic metabolism.

Air↗
PubMed2001

The potato tuber transcriptome: analysis of 6077 expressed sequence tags.

This is the first report of the biosynthetic potential of a tuber storage organ investigated by expressed sequence tag sequencing. A cDNA library was generated from the mature tuber of field grown potato (Solanum tuberosum var. Kuras). Partial sequences obtained from 6077 clones were assembled into 828 clusters and 1533 singletons. The average read length was 592 bp, and 2254 clones were full length. 5717 clones showed homology to genes from other organisms. Genes involved in protein synthesis, protein destination and cell defense predominated in tuber compared to stolon, shoot and leaf organs. 1063 clones were unique to tuber. Transcripts of starch metabolizing enzymes showed similar relative levels in tuber and stolon.

Expressed Sequence Tags↗
PubMed2003

The poplar root transcriptome: analysis of 7000 expressed sequence tags.

To date, most poplar expressed sequence tags (ESTs) are from above-ground tissues such as wood, leaf and buds. Here, we present a large-scale production of ESTs from roots of the hybrid cottonwood, Populus trichocarpaxdeltoides. cDNA libraries were generated from the root system of 2-month-old rooted cuttings, and roots of 2.5-month-old cuttings water-stressed for 19 days. Partial sequences obtained from 7013 clones were assembled into 1347 clusters and 3527 singletons. This set of ESTs represents 4874 unique transcripts expressed in roots. Putative functions could be assigned to 3021 (62%) of the transcripts. A significant portion of the ESTs encode proteins of common metabolic pathways; energy and metabolism represented 5% and 8% of total transcripts, respectively. Of specific interest to root functions are the 6% of ESTs involved in signalling pathways and hormone metabolism, and 4% encoding transporters and channels. The current poplar root ESTs and the aspen root ESTs present in public databases represent 6700 unique transcripts. The Unigene set was selected from the ESTs and used to generate nylon microarrays. Changes in aquaporins and transporter transcripts were then studied during adventitious root development.

Aquaporins↗