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Results for “Comparative transcriptomics”

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PubMed2004

Plasticity of mouse renal collecting duct in response to potassium depletion.

Plasticity of mouse renal collecting duct in response to potassium depletion.--Renal collecting ducts are the main sites for regulation of whole body potassium balance. Changes in dietary intake of potassium induce pleiotropic adaptations of collecting duct cells, which include alterations of ion and water transport properties along with an hypertrophic response. To study the pleiotropic adaptation of the outer medullary collecting duct (OMCD) to dietary potassium depletion, we combined functional studies of renal function (ion, water, and acid/base handling), analysis of OMCD hypertrophy (electron microscopy) and hyperplasia (PCNA labeling), and large scale analysis of gene expression (transcriptome analysis). The transcriptome of OMCD was compared in mice fed either a normal or a potassium-depleted diet for 3 days using serial analysis of gene expression (SAGE) adapted for downsized extracts. SAGE is based on the generation of transcript-specific tag libraries. Approximately 20,000 tags corresponding to 10,000 different molecular species were sequenced in each library. Among the 186 tags differentially expressed (P < 0.05) between the two libraries, 120 were overexpressed and 66 were downregulated. The SAGE expression profile obtained in the control library was representative of different functional classes of proteins and of the two cell types (principal and alpha-intercalated cells) constituting the OMCD. Combined with gene expression analysis, results of functional and morphological studies allowed us to identify candidate genes for distinct physiological processes modified by potassium depletion: sodium, potassium, and water handling, hyperplasia and hypertrophy. Finally, comparison of mouse and human OMCD transcriptomes allowed us to address the question of the relevance of the mouse as a model for human physiology and pathophysiology.

Acid-Base Equilibrium↗

PubMed2005

Circadian profiling of the transcriptome in immortalized rat SCN cells.

Endogenous oscillations in gene expression are a prevalent feature of the circadian clock in the mammalian suprachiasmatic nucleus (SCN) and similar timekeeping systems in other organisms. To determine whether immortalized cells derived from the rat SCN (SCN2.2) retain these intrinsic rhythm-generating properties, oscillatory behavior of the SCN2.2 transcriptome was analyzed and compared with that found in the rat SCN in vivo using rat U34A Affymetrix GeneChips. In SCN2.2 cells, 116 unique genes and 46 ESTs or genes of unknown function exhibited circadian fluctuations with a 1.5-fold or greater difference in their mRNA abundance for two cycles. Many (35%) of these rhythmically regulated genes in SCN2.2 cells also exhibited circadian profiles of mRNA expression in the rat SCN in vivo. Functional analyses and cartography indicate that a diverse set of cellular pathways are strategically regulated by the circadian clock in SCN2.2 cells and that the largest categories of rhythmic genes are those involved in cellular and systems-level communication or in metabolic processes like cellular respiration, fatty acid recycling, and steroid synthesis. Because many of the same genes or nodes within these functional categories were rhythmically expressed in both SCN2.2 cells and the rat SCN, the circadian regulation of these pathways may be important in modulating input to or output from the SCN clock mechanism. In summary, global expression and circadian regulation of the SCN2.2 transcriptome retain many SCN-like properties, suggesting that genes displaying rhythmic profiles in both experimental models may be integral to their function as both circadian oscillators and pacemakers.

Animals↗

PubMed2006

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtype-specific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers.

Carcinoma, Non-Small-Cell Lung↗

PubMed2006

Molecular dynamics of the Shewanella oneidensis response to chromate stress.

Temporal genomic profiling and whole-cell proteomic analyses were performed to characterize the dynamic molecular response of the metal-reducing bacterium Shewanella oneidensis MR-1 to an acute chromate shock. The complex dynamics of cellular processes demand the integration of methodologies that describe biological systems at the levels of regulation, gene and protein expression, and metabolite production. Genomic microarray analysis of the transcriptome dynamics of midexponential phase cells subjected to 1 mm potassium chromate (K(2)CrO(4)) at exposure time intervals of 5, 30, 60, and 90 min revealed 910 genes that were differentially expressed at one or more time points. Strongly induced genes included those encoding components of a TonB1 iron transport system (tonB1-exbB1-exbD1), hemin ATP-binding cassette transporters (hmuTUV), TonB-dependent receptors as well as sulfate transporters (cysP, cysW-2, and cysA-2), and enzymes involved in assimilative sulfur metabolism (cysC, cysN, cysD, cysH, cysI, and cysJ). Transcript levels for genes with annotated functions in DNA repair (lexA, recX, recA, recN, dinP, and umuD), cellular detoxification (so1756, so3585, and so3586), and two-component signal transduction systems (so2426) were also significantly up-regulated (p < 0.05) in Cr(VI)-exposed cells relative to untreated cells. By contrast, genes with functions linked to energy metabolism, particularly electron transport (e.g. so0902-03-04, mtrA, omcA, and omcB), showed dramatic temporal alterations in expression with the majority exhibiting repression. Differential proteomics based on multidimensional HPLC-MS/MS was used to complement the transcriptome data, resulting in comparable induction and repression patterns for a subset of corresponding proteins. In total, expression of 2,370 proteins were confidently verified with 624 (26%) of these annotated as hypothetical or conserved hypothetical proteins. The initial response of S. oneidensis to chromate shock appears to require a combination of different regulatory networks that involve genes with annotated functions in oxidative stress protection, detoxification, protein stress protection, iron and sulfur acquisition, and SOS-controlled DNA repair mechanisms.

Anion Transport Proteins↗

PubMed2005

AMOD: a morpholino oligonucleotide selection tool.

AMOD is a web-based program that aids in the functional evaluation of nucleotide sequences through sequence characterization and antisense morpholino oligonucleotide (target site) selection. Submitted sequences are analyzed by translation initiation site prediction algorithms and sequence-to-sequence comparisons; results are used to characterize sequence features required for morpholino design. Within a defined subsequence, base composition and homodimerization values are computed for all putative morpholino oligonucleotides. Using these properties, morpholino candidates are selected and compared with genomic and transcriptome databases with the goal to identify target-specific enriched morpholinos. AMOD has been used at the University of Minnesota to design approximately 200 morpholinos for a functional genomics screen in zebrafish. The AMOD web server and a tutorial are freely available to both academic and commercial users at http://www.secretomes.umn.edu/AMOD/.

DNA Primers↗

PubMed2004

Functional specialization amongst the Arabidopsis Toc159 family of chloroplast protein import receptors.

The initial stages of preprotein import into chloroplasts are mediated by the receptor GTPase Toc159. In Arabidopsis thaliana, Toc159 is encoded by a small gene family: atTOC159, atTOC132, atTOC120, and atTOC90. Phylogenetic analysis suggested that at least two distinct Toc159 subtypes, characterized by atToc159 and atToc132/atToc120, exist in plants. atTOC159 was strongly expressed in young, photosynthetic tissues, whereas atTOC132 and atTOC120 were expressed at a uniformly low level and so were relatively prominent in nonphotosynthetic tissues. Based on the albino phenotype of its knockout mutant, atToc159 was previously proposed to be a receptor with specificity for photosynthetic preproteins. To elucidate the roles of the other isoforms, we characterized Arabidopsis knockout mutants for each one. None of the single mutants had strong visible phenotypes, but toc132 toc120 double homozygotes appeared similar to toc159, indicating redundancy between atToc132 and atToc120. Transgenic complementation studies confirmed this redundancy but revealed little functional overlap between atToc132/atToc120 and atToc159 or atToc90. Unlike toc159, toc132 toc120 caused structural abnormalities in root plastids. Furthermore, when proteomics and transcriptomics were used to compare toc132 with ppi1 (a receptor mutant that is specifically defective in the expression, import, and accumulation of photosynthetic proteins), major differences were observed, suggesting that atToc132 (and atToc120) has specificity for nonphotosynthetic proteins. When both atToc159 and the major isoform of the other subtype, atToc132, were absent, an embryo-lethal phenotype resulted, demonstrating the essential role of Toc159 in the import mechanism.

Arabidopsis↗

PubMed2025

Adaptive Evolution for Freshwater Adaptation in Coilia nasus by Directional Selection on Osmoregulation Genes.

The molecular mechanisms underlying the adaptation to freshwater habitats in fish of marine origin remain unclear. Grenadier anchovies, such as Coilia nasus, originate from marine environments and include both anadromous and freshwater-resident conspecifics, making them ideal for studying adaptive evolution from marine to freshwater habitats. We conducted a comparative population genomic and transcriptome analysis of two distinct C. nasus lineages, one anadromous and the other freshwater-resident, collected from mainstream and estuarine regions of the Yangtze River, China. By genome-wide genotyping of the anadromous and the freshwater-resident populations, we observed significant divergence in osmoregulation, energy metabolism, and immune response pathways associated with ecological adaptation and energy expenditure for migration. Some ion transport genes such as CAMK1, ATP1α3, KCNJ1 and SLC30A2 were identified that may contribute to freshwater adaptation. Notably, numerous mineralocorticoid signalling genes (e.g., NR3C2, SGK1, ATP1α3, KCNJ1) exhibit dynamic change between the anadromous and freshwater populations, suggesting an important role for the hormone cortisol in regulating salinity acclimation in euryhaline fish. Among these genes, the ion channel ATP1α3 experienced adaptive amino acid substitutions (Val317Ile and Thr329Ser), which appear to be evolutionary hotspots across migratory species based on ortholog comparisons. These variants may facilitate sodium/potassium transport and highlight salinity tolerance as a key driver of divergence in anadromous fish transitioning to freshwater. These results enhance our understanding of the genetic basis underlying freshwater adaptation for an anadromous fish across osmotic boundaries.

Animals↗

PubMed2005

Transcriptome analysis of Pseudomonas aeruginosa growth: comparison of gene expression in planktonic cultures and developing and mature biofilms.

The transcriptomes of logarithmic- and stationary-phase Pseudomonas aeruginosa planktonic cultures and static biofilms of different stages of development were compared. Developing and confluent biofilm transcriptomes were found to be related to those of logarithmic- and stationary-phase planktonic cultures, respectively. In addition, a number of novel genes were up-regulated in developing and confluent biofilms, including genes encoding putative solute transport proteins and transcriptional regulators, respectively.

Bacterial Proteins↗

PubMed2006

Th1 response and cytotoxicity genes are down-regulated in cutaneous T-cell lymphoma.

PURPOSE: Increased production of Th2 cytokines characterizes Sezary syndrome, the leukemic form of cutaneous T-cell lymphomas (CTCL). To identify the molecular background and to study whether shared by the most common CTCL subtype, mycosis fungoides, we analyzed the gene expression profiles in both subtypes. EXPERIMENTAL DESIGN: Freshly isolated cells from 30 samples, representing skin, blood, and enriched CD4(+) cell populations of mycosis fungoides and Sezary syndrome, were analyzed with Affymetrix (Santa Clara, CA) oligonucleotide microarrays, quantitative PCR, or immunohistochemistry. The gene expression profiles were combined with findings of comparative genomic hybridization of the same samples to identify chromosomal changes affecting the aberrant gene expression. RESULTS: We identified a set of Th1-specific genes [e.g., TBX21 (T-bet), NKG7, and SCYA5 (RANTES)] to be down-regulated in Sezary syndrome as well as in a proportion of mycosis fungoides samples. In both Sezary syndrome and mycosis fungoides blood samples, the S100P and LIR9 gene expression was up-regulated. In lesional skin, IL7R and CD52 were up-regulated. Integration of comparative genomic hybridization and transcriptomic data identified chromosome arms 1q, 3p, 3q, 4q, 12q, 16p, and 16q as likely targets for new CTCL-associated gene aberrations. CONCLUSIONS: Our findings revealed several new genes involved in CTCL pathogenesis and potential therapeutic targets. Down-regulation of a set of genes involved in Th1 polarization, including the major Th1-polarizing factor, TBX21, was for the first time associated with CTCL. In addition, a plausible explanation for the proliferative response of CTCL cells to locally produced interleukin-7 was revealed.

Cytotoxicity, Immunologic↗

PubMed2006

Global transcriptome analysis of genetically identified neurons in the adult cortex.

The enormous cellular complexity of the brain is a major obstacle for gene expression profiling of neurological disease models, because physiologically relevant changes of transcription in a specific neuronal subset are likely to be lost in the presence of other neurons and glia. We solved this problem in transgenic mice by labeling genetically defined cells with a nuclear variant of GFP. When combined with laser-directed microdissection, intact RNA from unfixed, freeze-dried sections can be isolated, which is a prerequisite for high-quality global transcriptome analysis. Here, we compared gene expression profiles between pyramidal motor neurons and pyramidal somatosensory neurons captured from layer V of the adult neocortex. One striking feature of motor neurons is the elevated expression of ribosomal genes and genes involved in ATP synthesis. This suggests a molecular adaptation of the upper motor neurons to longer axonal projections and higher electrical activity. These molecular signatures were not detected when cortical layers and microareas were analyzed in toto. Additionally, we used microarrays to determine the global mRNA expression profiles of microdissected Purkinje cells and cellularly complex cerebellar cortex microregions. In summary, our analysis shows that cellularly complex targets lead to averaged gene expression profiles that lack substantial amounts of cell type-specific information. Thus, cell type-restricted sampling strategies are mandatory in the CNS. The combined use of a genetic label with laser-microdissection offers an unbiased approach to map patterns of gene expression onto practically any cell type of the brain.

Adenosine Triphosphate↗

PubMedDate not supplied

The use of microarrays for studying the pathogenesis of Helicobacter pylori.

At present, the genomes of various microorganisms have been completely sequenced, and many others are in progress. The availability of this level of information and the computational analysis of the described sequences have led to the development of new genomic areas such as: analysis in silico, comparative genomics, functional genomics, transcriptomics, proteomics, and pharmacogenomics. Microarray technology is a powerful tool for analyzing the expression profile of thousands of genes in a global way and can be applied to the study of various biological systems. Using the complete sequences for both the H. pylori and human genome that are available in the data bases, a number of researchers have revealed important information. Some of these data offer a glimpse into the great genetic diversity of H. pylori, the differential genetic expression between the strains that shows the complexity of the response of microorganisms to different conditions of development, and into the association of gene cluster expression with clinical outcome. Other groups have examined the global transcriptional response of gastric epithelial cells to H. pylori. The majority of these studies report an alteration in gene expression related to transcription functions, transduction signals, cell cycle regulation and differentiation, development factors, proliferation/apoptosis balance, expression of membrane proteins, and inflammatory response.

Animals↗

PubMed2004

Epithelial cell preparation for proteomic and transcriptomic analysis in human pancreatic tissue.

Standardized sample preparation procedures constitute a prerequisite for obtaining reliable and reproducible results in gene expression research in humans. In particular, in diseases such as pancreatic cancer and pancreatitis, isolating epithelial cells is an important step preceding such research. In pancreatic tissue, the high amount of RNAases is a further problem when it comes to obtaining high-quality RNA, and the presence of secreted proteases accelerates protein degradation. We developed a successful method that addresses these different problems. This method, which uses epithelial cell surface antibody Ber-Ep4, proteases, and RNAases inhibitors, leads to a significant enrichment (> 95% purity) of epithelial cells from fresh human tissue samples and allows for both proteomics (Western Blot, 2D PAGE) and transcriptomics studies (rtPCR, cDNA microarray). Compared with other cell purification procedures, this method is characterized by several advantages: a large quantity of cells available for downstream analysis, combined transcriptomics and proteomics studies using the same samples, better reproducibility of proteomics studies, and an acceptable yield (63%) for gene expression arrays studies. Moreover, a quality control protocol addressing the needs of the industry and the requirements of regulatory agencies is proposed.

Epithelial Cells↗

PubMed2002

Comparative analysis of human genome assemblies reveals genome-level differences.

Previous comparative analysis has revealed a significant disparity between the predicted gene sets produced by the International Human Genome Sequencing Consortium (HGSC) and Celera Genomics. To determine whether the source of this discrepancy was due to underlying differences in the genomic sequences or different gene prediction methodologies, we analyzed both genome assemblies in parallel. Using the GENSCAN gene prediction algorithm, we generated predicted transcriptomes that could be directly compared. BLAST-based comparisons revealed a 20-30% difference between the transcriptomes. Further differences between the two genomes were revealed with protein domain PFAM analyses. These results suggest that fundamental differences between the two genome assemblies are likely responsible for a significant portion of the discrepancy between the transcript sets predicted by the two groups.

Chromosome Mapping↗

PubMed2005

Breakpoint analysis of the pericentric inversion between chimpanzee chromosome 10 and the homologous chromosome 12 in humans.

During this study, we analysed the pericentric inversion that distinguishes human chromosome 12 (HSA12) from the homologous chimpanzee chromosome (PTR10). Two large chimpanzee-specific duplications of 86 and 23 kb were observed in the breakpoint regions, which most probably occurred associated with the inversion. The inversion break in PTR10p caused the disruption of the SLCO1B3 gene in exon 11. However, the 86-kb duplication includes the functional SLCO1B3 locus, which is thus retained in the chimpanzee, although inverted to PTR10q. The second duplication spans 23 kb and does not contain expressed sequences. Eleven genes map to a region of about 1 Mb around the breakpoints. Six of these eleven genes are not among the differentially expressed genes as determined previously by comparing the human and chimpanzee transcriptome of fibroblast cell lines, blood leukocytes, liver and brain samples. These findings imply that the inversion did not cause major expression differences of these genes. Comparative FISH analysis with BACs spanning the inversion breakpoints in PTR on metaphase chromosomes of gorilla (GGO) confirmed that the pericentric inversion of the chromosome 12 homologs in GGO and PTR have distinct breakpoints and that humans retain the ancestral arrangement. These findings coincide with the trend observed in hominoid karyotype evolution that humans have a karyotype close to an ancestral one, while African great apes present with more derived chromosome arrangements.

Animals↗

PubMed2003

From transcriptome to proteome: differentially expressed proteins identified in synovial tissue of patients suffering from rheumatoid arthritis and osteoarthritis by an initial screen with a panel of 791 antibodies.

Global scale molecular profiling of diseased tissues is an important first step to unravel candidate target molecules that are involved in the pathogenesis of a disease. We have performed a comparative molecular characterization at the transcriptome (microarray with 12 526 gene specificities) and proteome level (multi-Western blot PowerBlot with 791 antibodies) of synovial tissue from rheumatoid arthritis (RA) compared to osteoarthritis (OA) patients. From the panel of 791 antibodies, 260 (33%) detected their corresponding protein. Out of 58 unambiguous changes at the protein level only 16 coincided at the transcript level (28%). Stat1, p47phox and manganese superoxide dismutase were shown to be reproducibly overexpressed in RA versus OA synovial tissue by Western blots with a panel of 8 RA versus 8 OA samples. Cathepsin D was among the most prominent proteins scored to be underexpressed in RA by the PowerBlot whereas no differences of the respective transcript were observed. The lower abundance of cathepsin D protein in RA compared to OA tissue was also reproduced in other patient samples. Immunohistochemistry assigned the Stat1 protein in RA synovial tissue mainly to macrophages and T lymphocytes and the p47phox protein in particular to macrophages. In conclusion, our approach provided us with new candidate molecules for further analysis of rheumatic diseases and stressed the importance of studies at the protein level.

Antibodies↗

PubMed2026

Integrative ATAC-seq and RNA-seq analysis reveals lactation performance between Sewa sheep and East Friesian sheep.

Lactation performance is a pivotal economic trait in sheep production, yet its underlying epigenetic regulatory mechanisms remain poorly understood. In the present study, we integrated ATAC-seq and RNA-seq to compare chromatin accessibility landscapes and transcriptomic in mammary gland tissues from Sewa sheep (SWS) and East Friesian sheep (EFS). Histological characterization revealed that SWS exhibited significantly smaller mammary acini area, smaller lipid droplet area, and reduced lipid droplet diameter compared to EFS. ATAC-seq analysis identified 15,902 differentially accessible regions (DARs) between the two breeds, with motif enrichment analysis uncovering key transcription factors potentially governing lactation traits. RNA-seq analysis revealed 1,163 differentially expressed genes (DEGs), which were involved in lactation regulation. Integrated analysis identified 441 overlapping genes, and enriched in glycolysis/gluconeogenesis (e.g., PGAM1, ENO1) and pyruvate metabolism (e.g., ACACA, ACSS1, ACYP1). Collectively, our study provides new insights into the epigenetic regulatory mechanisms underlying lactation performance differences in sheep.

Animals↗

PubMed2024

RNAseq analysis of oocyte maturation from the germinal vesicle stage to metaphase II in pig and human.

During maturation oocytes at the germinal vesicle (GV) stage progress to metaphase II (MII). However, during in vitro maturation a proportion often fail to progress. To understand these processes, we employed RNA sequencing to examine the transcriptome profile of these three groups of oocytes from the pig. We compared our findings with similar public oocyte data from humans. The transcriptomes in oocytes that failed to progress was similar to those that did. We found in both species, the most upregulated genes in MII oocytes were associated with chromosome segregation and cell cycle processes, while the most down regulated genes were relevant to ribosomal and mitochondrial pathways. Moreover, those genes involved in chromosome segregation during GV to MII transition were conserved in pig and human. We also compared MII and GV oocyte transcriptomes at the isoform transcript level in both species. Several thousands of genes (including DTNBP1, MAPK1, RAB35, GOLGA7, ATP1A1 and ATP2B1) identified as not different in expression at a gene transcript level were found to have differences in isoform transcript levels. Many of these genes were involved in ATPase-dependent or GTPase-dependent intracellular transport in pig and human, respectively. In conclusion, our study suggests the failure to progress to MII in vitro may not be regulated at the level of the genome and that many genes are differentially regulated at the isoform level, particular those involved ATPase- or GTPase-dependent intracellular transport.

Humans↗

PubMed2006

Non-human primate fetal kidney transcriptome analysis indicates mammalian target of rapamycin (mTOR) is a central nutrient-responsive pathway.

Developmental programming is defined as the process by which gene-environment interaction in the developing organism leads to permanent changes in phenotype and function. Numerous reports of maternal nutrient restriction during pregnancy demonstrate altered renal development. Typically this alteration manifests as a reduction in the total number of glomeruli in the mature kidney of the offspring, and suggests that predisposition to develop chronic renal disease may include an in utero origin. In a previous study, we defined the transcriptome in the kidney from fetuses of control (CON, fed ad libitum) and nutrient-restricted (NR, fed 70% of CON starting at 0.16 gestation (G)) pregnancies at half-way through gestation (0.5G), and established transcriptome and morphological changes in NR kidneys compared to CON. One goal of the present study was to use transcriptome data from fetal kidneys of CON and NR mothers at 0.5G with histological data to identify the molecular mechanisms that may regulate renal development. A second goal was to identify mechanisms by which NR elicits its affect on fetal baboon kidney. We have used an end-of-pathway gene expression analysis to prioritize and identify key pathways regulating the 0.5G kidney phenotype in response NR. From these data we have determined that the mammalian target of rapamycin (mTOR) signalling pathway is central to this phenotype.

Animal Feed↗