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At least 1,189 records · Page 66Linked to original sources
PubMed2003

Homodirectional changes in transcriptome composition and mRNA translation induced by rapamycin and heat shock.

Transcription and mRNA turnover determine the quantitative composition of the cellular transcriptome. The transcriptome in turn serves as a template for the proteome via translation. Treatment of Saccharomyces cerevisiae with the TOR kinase inhibitor rapamycin causes increases and decreases in the mRNA levels of hundreds of genes. We used DNA microarray analysis to monitor simultaneously transcriptome and translational changes for all detectable yeast mRNAs. Notably, genes that are induced in the transcriptome correlate tightly with more efficiently translated mRNAs (based on their relative degree of polyribosome association); similarly, genes that show reduced mRNA levels after rapamycin treatment also show lower translational fitness. Microarray analyses on heat-shocked cells also reveal homodirectional co-regulatory responses. Thus, signal-induced changes in the transcriptome are amplified at the translational level. These results unveil a higher level of coordinated gene regulation that we refer to as 'potentiation.'

Enzyme Inhibitors↗
PubMed2025

Evolutionary fingerprints of epithelial-to-mesenchymal transition.

Mesenchymal plasticity has been extensively described in advanced epithelial cancers; however, its functional role in malignant progression is controversial1-5. The function of epithelial-to-mesenchymal transition (EMT) and cell plasticity in tumour heterogeneity and clonal evolution is poorly understood. Here we clarify the contribution of EMT to malignant progression in pancreatic cancer. We used somatic mosaic genome engineering technologies to trace and ablate malignant mesenchymal lineages along the EMT continuum. The experimental evidence clarifies the essential contribution of mesenchymal lineages to pancreatic cancer evolution. Spatial genomic analysis, single-cell transcriptomic and epigenomic profiling of EMT clarifies its contribution to the emergence of genomic instability, including events of chromothripsis. Genetic ablation of mesenchymal lineages robustly abolished these mutational processes and evolutionary patterns, as confirmed by cross-species analysis of pancreatic and other human solid tumours. Mechanistically, we identified that malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division. Thus, EMT favours the emergence of genomic-unstable, highly fit tumour cells, which strongly supports the concept of cell-state-restricted patterns of evolution, whereby cancer cell speciation is propagated to progeny within restricted functional compartments. Restraining the evolutionary routes through ablation of clones capable of mesenchymal plasticity, and extinction of the derived lineages, halts the malignant potential of one of the most aggressive forms of human cancer.

Animals↗
PubMed2026

Single-cell transcriptomics reveals distinct microglial state remodeling associated with the (R)-nicotine/diosmetin combination and galantamine in LPS-challenged BV2 cells.

BACKGROUND: Microglial neuroinflammation contributes to the progression of neurodegenerative diseases, yet it remains challenging to attenuate inflammatory responses while preserving cellular function. The effects of (R)-nicotine, diosmetin, their combined administration, and galantamine on heterogeneous BV2 transcriptional states have not been compared at single-cell resolution. METHODS: LPS-stimulated BV2 microglial-like cells were treated with (R)-nicotine, diosmetin, their combination (DR), or galantamine. Single-cell RNA sequencing was performed with three biological replicates per group and integrated with RNA velocity and SCENIC regulon inference to characterize treatment-associated state redistribution, inferred local transcriptional directionality and regulon-activity patterns. Functional validation included CCK-8 metabolic activity assays, multiplex cytokine ELISA, BDNF/GDNF quantification, qPCR, and high-content immunofluorescence analysis of iNOS and Arg1 at single-cell resolution. RESULTS: LPS decreased the relative abundance of the Itgae+/Plk4+ cluster while increasing the Nmur1+/Limk2+ cluster and inflammatory effector programs. DR treatment suppressed pro-inflammatory cytokine release without significantly reducing CCK-8-assessed metabolic activity, increased the Itgae+/Plk4+ cluster proportion, and increased BDNF/GDNF relative to LPS. RNA velocity and SCENIC analyses suggested that DR and galantamine showed distinct transcriptional and regulatory patterns: DR attenuated Batf-associated inflammatory regulons and was associated with increased Atf3-linked stress-response activity, whereas galantamine preferentially engaged DNA repair and genome-maintenance programs. CONCLUSION: These findings indicate that the DR condition was associated with remodeling of LPS-challenged BV2 microglial-like states, attenuation of inflammatory programs, and increased neurotrophic outputs relative to LPS, without significantly reducing CCK-8-assessed metabolic activity. This study provides a single-cell characterization of distinct treatment-associated responses to (R)-nicotine, diosmetin, their combined administration, and galantamine.

Microglia↗
PubMed2005

Genomic medicine: genetic variation and its impact on the future of health care.

Advances in genome technology and other fruits of the Human Genome Project are playing a growing role in the delivery of health care. With the development of new technologies and opportunities for large-scale analysis of the genome, transcriptome, proteome and metabolome, the genome sciences are poised to have a profound impact on clinical medicine. Cancer prognostics will be among the first major test cases for a genomic medicine paradigm, given that all cancer is caused by genomic instability, and microarrays allow assessment of patients' entire expressed genomes. Analysis of breast cancer patients' expression patterns can already be highly correlated with recurrence risks. By integrating clinical data with gene expression profiles, imaging, metabolomic profiles and proteomic data, the prospect for developing truly individualized care becomes ever more real. Notwithstanding these promises, daunting challenges remain for genomic medicine. Success will require planning robust prospective trials, analysing health care economic and outcome data, assuaging insurance and privacy concerns, developing health delivery models that are commercially viable and scaling up to meet the needs of the whole population.

Delivery of Health Care↗
PubMed2005

Group A Streptococcus transcriptome dynamics during growth in human blood reveals bacterial adaptive and survival strategies.

The molecular basis for bacterial responses to host signals during natural infections is poorly understood. The gram-positive bacterial pathogen group A Streptococcus (GAS) causes human mucosal, skin, and life-threatening systemic infections. During the transition from a throat or skin infection to an invasive infection, GAS must adapt to changing environments and host factors. To better understand how GAS adapts, we used transcript profiling and functional analysis to investigate the transcriptome of a wild-type serotype M1 GAS strain in human blood. Global changes in GAS gene expression occur rapidly in response to human blood exposure. Increased transcription was observed for many genes that likely enhance bacterial survival, including those encoding superantigens and host-evasion proteins regulated by a multiple gene activator called Mga. GAS also coordinately expressed genes involved in proteolysis, transport, and catabolism of oligopeptides to obtain amino acids in this protein-rich host environment. Comparison of the transcriptome of the wild-type strain to that of an isogenic deletion mutant (DeltacovR) mutated in the two-component regulatory system designated CovR-CovS reinforced the hypothesis that CovR-CovS has an important role linking key biosynthetic, catabolic, and virulence functions during transcriptome restructuring. Taken together, the data provide crucial insights into strategies used by pathogenic bacteria for thwarting host defenses and surviving in human blood.

DNA, Complementary↗
PubMed2001

Regulation of the Arabidopsis transcriptome by oxidative stress.

Oxidative stress, resulting from an imbalance in the accumulation and removal of reactive oxygen species such as hydrogen peroxide (H(2)O(2)), is a challenge faced by all aerobic organisms. In plants, exposure to various abiotic and biotic stresses results in accumulation of H(2)O(2) and oxidative stress. Increasing evidence indicates that H(2)O(2) functions as a stress signal in plants, mediating adaptive responses to various stresses. To analyze cellular responses to H(2)O(2), we have undertaken a large-scale analysis of the Arabidopsis transcriptome during oxidative stress. Using cDNA microarray technology, we identified 175 non-redundant expressed sequence tags that are regulated by H(2)O(2). Of these, 113 are induced and 62 are repressed by H(2)O(2). A substantial proportion of these expressed sequence tags have predicted functions in cell rescue and defense processes. RNA-blot analyses of selected genes were used to verify the microarray data and extend them to demonstrate that other stresses such as wilting, UV irradiation, and elicitor challenge also induce the expression of many of these genes, both independently of, and, in some cases, via H(2)O(2).

Adaptation, Physiological↗
PubMed2003

Small amplified RNA-SAGE: an alternative approach to study transcriptome from limiting amount of mRNA.

Serial analysis of gene expression (SAGE) is a widely used and powerful technique to characterize and compare transcriptomes. Although several modifications have been proposed to the initial protocol with the aim of reducing the amount of starting material, unless additional PCR steps are added, the technique is still limited by the need for at least 1 micro g of total RNA. As extra PCR amplification might introduce representation biases, current SAGE protocols are not fully suitable for the study of small, microdissected tissue samples. We propose here an alternative method involving the linear amplification of small mRNA fragments containing the SAGE tags. The procedure allows preparation of libraries of over 100 000 tags from as few as 2500 cells. A satisfactory correlation was observed between a microSAGE library made from 5 microg of total thyroid RNA, and a library prepared from 50 ng of the same RNA preparation according to the present protocol.

Animals↗
PubMed2025

Integrated proteomic network analysis reveals PTPRC as a central hub protein orchestrating co-expression modules and metabolic dysregulation in renal carcinoma: PTPRC protein molecular action.

The occurrence of renal carcinoma is closely related to a variety of molecular mechanisms and metabolic disorders. PTPRC (protein tyrosine phosphatase receptor C), as an important regulatory protein, was studied to reveal the role of PTPRC in renal carcinoma through comprehensive proteomic network analysis, especially its core position in the coordination of co-expression modules and metabolic disorders. This study was the first to download and process multiple publicly available renal cancer transcriptome data to conduct differential gene expression analysis across datasets. Functional enrichment and disease ontology analysis were performed on the transcriptome of renal cancer, and weighted gene co-expression network (WGCNA) was constructed. The results showed that comprehensive principal component analysis revealed significant differences in the transcriptome of renal cancer, and functional annotation revealed specific pathways associated with renal cancer. WGCNA analysis identified tumor-associated co-expression modules, while multi-omics analysis further identified core regulatory networks including PTPRC. As a central hub protein, PTPRC plays an important coordinating role in the co-expression module and metabolic dysregulation of renal carcinoma. This discovery provides a new perspective for understanding the molecular mechanism of kidney cancer.

Humans↗
PubMed2024

Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach.

Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.

Kidney Neoplasms↗
PubMed2006

Comprehensive transcriptional profiling of NaCl-stressed Arabidopsis roots reveals novel classes of responsive genes.

BACKGROUND: Roots are an attractive system for genomic and post-genomic studies of NaCl responses, due to their primary importance to agriculture, and because of their relative structural and biochemical simplicity. Excellent genomic resources have been established for the study of Arabidopsis roots, however, a comprehensive microarray analysis of the root transcriptome following NaCl exposure is required to further understand plant responses to abiotic stress and facilitate future, systems-based analyses of the underlying regulatory networks. RESULTS: We used microarrays of 70-mer oligonucleotide probes representing 23,686 Arabidopsis genes to identify root transcripts that changed in relative abundance following 6 h, 24 h, or 48 h of hydroponic exposure to 150 mM NaCl. Enrichment analysis identified groups of structurally or functionally related genes whose members were statistically over-represented among up- or down-regulated transcripts. Our results are consistent with generally observed stress response themes, and highlight potentially important roles for underappreciated gene families, including: several groups of transporters (e.g. MATE, LeOPT1-like); signalling molecules (e.g. PERK kinases, MLO-like receptors), carbohydrate active enzymes (e.g. XTH18), transcription factors (e.g. members of ZIM, WRKY, NAC), and other proteins (e.g. 4CL-like, COMT-like, LOB-Class 1). We verified the NaCl-inducible expression of selected transcription factors and other genes by qRT-PCR. CONCLUSION: Microarray profiling of NaCl-treated Arabidopsis roots revealed dynamic changes in transcript abundance for at least 20% of the genome, including hundreds of transcription factors, kinases/phosphatases, hormone-related genes, and effectors of homeostasis, all of which highlight the complexity of this stress response. Our identification of these transcriptional responses, and groups of evolutionarily related genes with either similar or divergent transcriptional responses to stress, will facilitate mapping of regulatory networks and extend our ability to improve salt tolerance in plants.

Arabidopsis↗
PubMed2025

Time-course transcriptome and proteomic dynamics during the de novo shoot organogenesis in Chinese fir (Cunninghamia lanceolata).

De novo shoot organogenesis (DNSO) enables plants to regenerate shoots from various explants, offering valuable opportunities for research and plant biotechnology applications. While significant progress has been made in understanding regeneration in angiosperms, the regulatory mechanisms in gymnosperms, particularly Chinese fir (Cunninghamia lanceolata), remain poorly understood, despite its importance as a key timber species in China. This study successfully established an efficient DNSO protocol for Chinese fir, identifying six distinct stages in the process through cellular-level analysis. Time-course transcriptome and proteomics analyses revealed dynamic changes in mRNA and protein levels during regeneration. Notably, proteins showed more significant alterations across a broad range of biological processes, often independent of corresponding mRNA changes. Key pathways associated with ethylene metabolism and abiotic stress responses were enriched, highlighting their critical roles in regeneration. Further experiments confirmed that moderate osmotic stress treatments (150 mm mannitol) and ethylene treatment (100 μm ACC and 5 μm AgNO3) substantially enhanced DNSO efficiency. In summary, this study uncovers the molecular mechanisms underlying Chinese fir DNSO, providing valuable insights into improving plant regeneration efficiency in this economically important species. These findings contribute to advancements in plant biotechnology and sustainable forestry practices.

Cunninghamia↗
PubMed2006

On the way to understand biological complexity in plants: S-nutrition as a case study for systems biology.

The establishment of technologies for high-throughput DNA sequencing (genomics), gene expression (transcriptomics), metabolite and ion analysis (metabolomics/ionomics) and protein analysis (proteomics) carries with it the challenge of processing and interpreting the accumulating data sets. Publicly accessible databases and newly development and adapted bioinformatic tools are employed to mine this data in order to filter relevant correlations and create models describing physiological states. These data allow the reconstruction of networks of interactions of the various cellular components as enzyme activities and complexes, gene expression, metabolite pools or pathway flux modes. Especially when merging information from transcriptomics, metabolomics and proteomics into consistent models, it will be possible to describe and predict the behaviour of biological systems, for example with respect to endogenous or environmental changes. However, to capture the interactions of network elements requires measurements under a variety of conditions to generate or refine existing models. The ultimate goal of systems biology is to understand the molecular principles governing plant responses and consistently explain plant physiology.

Arabidopsis↗
PubMed2002

The yeast transcriptome in aerobic and hypoxic conditions: effects of hap1, rox1, rox3 and srb10 deletions.

The transcriptome of Saccharomyces cerevisiae was screened using the high-density membrane hybridization method, under aerobic and hypoxic conditions, in wild-type and mutant backgrounds obtained by the disruption of the genes encoding the regulatory proteins Hap1, Rox1 and the Srb10 and Rox3 subunits of RNA polymerase II holoenzyme. None of the mutations studied was able to fully overcome the wild-type hypoxic response. Deletion of the hap1 gene changed the expression profiles of individual open reading frames (ORFs) under both aerobic and hypoxic conditions. Major changes associated with rox3 deletion were related to the hypoxic activation. Rox3 also caused a repressor effect (oxygen-independent) on a subset of genes related to subtelomeric proteins. With regard to the effect brought about by the deletion of rox1 and srb10, correspondence cluster analysis revealed that the transcriptome profile in aerobic conditions is very similar in the wild-type and both deletion strains. In contrast, however, differences were found during hypoxia between the subgroup formed by wild-type and the Deltarox1 deletant compared with the Deltasrb10 deletant. An analysis of selected ORFs responding to hypoxia, in association with a dependence on the regulatory factors studied, made it possible to identify the clusters that are related to different regulatory circuits.

Aerobiosis↗
PubMed2004

[Novel molecular marker systems--SRAP and TRAP and their application].

SRAP and TRAP are two kinds of newly developed molecular marker systems with the advantages of simplicity, high throughput, numerous co-dominant makers, highly reproducibility and ready to sequence, especially preferential targeting ORFs. The principle and protocol of SRAP and TRAP, which were developed in Brassica and Helianthus crops firstly, are introduced in the paper. Primer design is a key step for SRAP and TRAP, and some F-and R-primers were developed. Unlike SRAP technique, the TRAP requires cDNA or EST sequence information for fixed primer development. The annealing temperature is 35 degrees in the first 5 cycles and 50 degrees in the subsequent 30~35 cycles. The amplicons can be separated by polyacrylamide or agarose gel, and detected by autoradiography, silver or EB staining. SRAP and TRAP are applied in germplasm genetic diversity analysis, genetic map including transcriptome map construction, important trait gene tagging and gene cloning in many crops.

Acid Phosphatase↗
PubMed2024

Single cell RNA sequencing provides novel cellular transcriptional profiles and underlying pathogenesis of presbycusis.

Age-related hearing loss (ARHL) or presbycusis is associated with irreversible progressive damage in the inner ear, where the sound is transduced into electrical signal; but the detailed mechanism remains unclear. Here, we sought to determine the potential molecular mechanism involved in the pathogeneses of ARHL with bioinformatics methods. A single-cell transcriptome sequencing study was performed on the cochlear samples from young and aged mice. Detection of identified cell type marker allowed us to screen 18 transcriptional clusters, including myeloid cells, epithelial cells, B cells, endothelial cells, fibroblasts, T cells, inner pillar cells, neurons, inner phalangeal cells, and red blood cells. Cell-cell communications were analyzed between young and aged cochlear tissue samples by using the latest integration algorithms Cellchat. A total of 56 differentially expressed genes were screened between the two groups. Functional enrichment analysis showed these genes were mainly involved in immune, oxidative stress, apoptosis, and metabolic processes. The expression levels of crucial genes in cochlear tissues were further verified by immunohistochemistry. Overall, this study provides new theoretical support for the development of clinical therapeutic drugs.

Animals↗
PubMed2006

Mechanisms of patulin toxicity under conditions that inhibit yeast growth.

Patulin, 4-hydroxy-4H-furo[3,2c]pyran-2(6H)-one, is one of the best characterized and most widely disseminated mycotoxins found in agricultural products. Nonetheless, the mechanisms by which patulin causes toxicity are not well understood. Thus, the cytotoxicity of patulin was characterized by analysis of the yeast transcriptome upon challenge with patulin. Interestingly, patulin-induced yeast gene expression profiles were found to be similar to gene expression patterns obtained after treatment with the antifungal agricultural chemicals thiuram, maneb, and zineb. Moreover, patulin treatment was found to activate protein degradation, especially proteasome activities, sulfur amino acid metabolism, and the defense system for oxidative stress. Damage to DNA by alkylation was also suggested, and this seemed to be repaired by recombinational and excision repair mechanisms. Furthermore, the results provide potential biomarker genes for the detection of patulin in agricultural products. The results suggest the possibility of applying the yeast transcriptome system for the evaluation of chemicals, especially for natural chemicals that are difficult to get by organic synthesis.

Amino Acids, Sulfur↗
PubMed2005

True and false discovery in DNA microarray experiments: transcriptome changes in the hippocampus of presenilin 1 mutant mice.

In transcriptome profiling experiments using DNA microarrays, it is critical to maximize putatively true data discovery while keeping the false discovery rate at acceptable levels. Using previously published and verified transcriptome datasets of mice with genetically altered PS1 physiology, we present a simple, robust, and system-specific assessment of type I and type II errors in two independent microarray experimental series. We provide evidence to suggest that for maximizing true discovery and minimizing false discovery, statistical criteria alone are inferior to statistical significance plus magnitude of change criteria. Furthermore, we found that, regardless of the exact criteria used for determining differential expression, different data extraction protocols give rise to different discovery and false discovery rates. In addition, a large proportion of expression differences were both dataset and analytical approach dependent. The data assessment methods presented and discussed in this manuscript can be easily carried out on any microarray dataset using basic spreadsheet functions as the only tool needed. Finally, we provide an in-depth analysis of the hippocampal transcriptome of DeltaE9 hPS1 transgenic mice and mice with a conditional ablation of the PS1 gene.

Animals↗
PubMed2025

MOADE: a multimodal autoencoder for dissociating bulk multi-omics data.

In single cell biology, the complexity of tissues may hinder lineage cell mapping or tumor microenvironment decomposition, requiring digital dissociation of bulk tissues. Many deconvolution methods focus on transcriptomic assay, not easily applicable to other omics due to ambiguous cell markers and reference-to-target difference. Here, we present MOADE, a multimodal autoencoder pipeline linking multi-dimensional features to jointly predict personalized multi-omic profiles and cellular compositions, using pseudo-bulk data constructed by internal non-transcriptomic reference and external scRNA-seq data. MOADE is evaluated through rigorous simulation experiments and real multi-omic data from multiple tissue types, outperforming nine deconvolution pipelines with superior generalizability and fidelity.

Humans↗