SEARCH · PubMed Health

Results for “Transcriptomic alterations”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources

PubMed2025

Balancing LncRNA H19 and miR-675 Bioconversion as a Key Regulator of Embryonic Myogenesis Under Maternal Obesity.

BACKGROUND: Maternal obesity (MO) impairs fetal skeletal muscle development, but the underlying mechanisms remain poorly defined. The regulatory roles of lncRNA H19 and its first exon derived microRNA675 (miR675) in prenatal muscle development remain to be examined. H19/Igf2 are in the same imprinting cluster with H19 expressed from the maternal allele while Igf2 expresses paternally. H19 contains a G-rich loop, and KH-type splicing regulatory protein (KHSRP) mediates the biogenesis of pre-miRNAs containing G-rich loops, which depends on its phosphorylation by AKT, a key mediator of IGF2 signalling. This study aims to depict the elusive function of these regulators that are affected by MO during embryonic myogenesis. METHODS: Single-cell transcriptomic sequencing and GeoMx spatial RNA sequencing were performed to identify the differentially expressed genes between embryos from MO and control (CT) mice. Both E11.5 and E13.5 embryos were collected and analysed to validate the sequencing data. The roles of H19 and miR657 in myogenesis were further analysed in P19 embryonic cells via CRISPR/dCas9-mediated H19 activation and inhibition. The epigenetic changes of H19 were analysed by methylated DNA immunoprecipitation, and allele-targeted analysis of H19 was performed by crossing C57BL/6J and CAST/EiJ mice. RESULTS: Transcriptomic analysis showed that MO embryos contained less differentiated myocytes (1.34%) than CT embryos (2.86%). Myogenesis-related GO biological processes were down-regulated in the MO embryonic myotome region. MO embryos showed lower expression of myogenic transcription factors such as Myf5, Myod1, Myog, Mef2c and Myh3 (p < 0.05). MO altered epigenetic modifications of the H19 genomic cluster, showing a decreased methylation level in H19 imprinting control region (p < 0.05) and a diallelic expression pattern of H19, which elevated its expression in MO embryos. Overexpression of H19 inhibited myogenesis in P19 cells, but miR675 promoted myogenesis, suggesting the critical regulatory roles of bioconversion of H19 to miR675. A KHSRP mediates the biogenesis of miR675, a process that relies on its phosphorylation by IGF2/AKT signalling. Knocking-down of KHSRP and inhibition of AKT abolished miR675 biogenesis. MO suppressed IGF2/AKT signalling and blocked KHSRP-dependent miR675 biogenesis in embryos. CONCLUSIONS: We found differential effects of H19 and miR675 on embryonic myogenesis. MO up-regulates H19 but blocks its miR675 bioconversion via suppressing IGF2/AKT/KHSRP signalling axis. Myogenesis in MO embryos was impeded due to the highly accumulated H19 and blocked miR675 biogenesis.

RNA, Long Noncoding↗

PubMed2006

Transcriptome profiling of Saccharomyces cerevisiae during a transition from fermentative to glycerol-based respiratory growth reveals extensive metabolic and structural remodeling.

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.

Adaptation, Physiological↗

PubMed2025

A prognostic signature for lung adenocarcinoma in people who have never smoked.

Knowledge of tumor cell dynamics can inform prognosis and treatment yet is largely lacking for lung adenocarcinoma in people who have never smoked (NS-LUAD). With RNA-seq data from 684 NS-LUAD and validation in an independent dataset, we identified three subtypes with distinct phenotypic traits and cell compositions. Additional genomic and histological data further characterized the subtypes. 'Steady', marked by low proliferation, high alveolar cell fraction, moderate-to-well differentiation, and fewer driver genes' alterations, is linked to prolonged survival and low immune evasion. 'Proliferative' shows high proliferation markers, TP53 mutations, and gene fusions. 'Chaotic', with high epithelial-to-mesenchymal transition markers, has the worst prognosis even within stage I tumors. Lacking known molecular or histological characteristics, this aggressive subtype is solely identified by transcriptomic data. A 60-gene signature recapitulates the overall classification and strongly predicts survival even within subgroups based on tumor stage or known genomic features, emphasizing its potential for improving NS-LUAD prognostication in clinical settings.

Journal Article↗

PubMed2006

Comparative transcriptome maps: a new approach to the diagnosis of colorectal carcinoma patients using cDNA microarrays.

The progression of colorectal cancer involves accumulation of various genetic and epigenetic events that dramatically change gene expression. The aim of this study was to investigate a possible new approach to the diagnosis of colorectal carcinoma patients, based on their gene expression profiles. Human 19K cDNA microarrays were used to analyze the gene expression profiles of 18 colorectal carcinoma patients. Transcriptome maps (TMs) were analyzed to detect chromosomal regions that could serve as potential diagnostic markers for colon cancer. A comparison of TMs showed chromosome regions with conserved changes of gene expression typical of colorectal cancer in general, and also patient-specific variable regions. We identified 195 genes with significantly altered expression in colon cancer. Functional analysis of the regulated genes distinguished three main categories: biological processes, cellular components, and molecular functions. We found that different patients had chromosome regions characterized by very similar changes of gene expression, probably linked to the most fundamental events in carcinogenesis. On the other hand, variable chromosome regions can be patient-specific. The variable regions may provide further information on the individual pathogenesis and prognosis of the patient. Comparison of TMs is proposed as a tool to facilitate diagnosis and treatment planning for individual patients.

Biomarkers, Tumor↗

PubMed2002

Sepsis gene expression profiling: murine splenic compared with hepatic responses determined by using complementary DNA microarrays.

OBJECTIVE: DNA microarrays allow genome-wide assessment of changes in relative messenger RNA abundance and thus can be used to monitor changes in gene expression. The aim of this series of experiments was to gain experience in sepsis gene expression profiling in a well-accepted model of murine polymicrobial abdominal sepsis and begin characterizing (in the parlance of genomics) the sepsis "transcriptome." DESIGN: Prospective animal study. SETTING: University-based animal research facility.SUBJECTS C57BL/6 mice. INTERVENTIONS: After induction of general anesthesia, cecal ligation and puncture were performed to induce peritonitis and polymicrobial sepsis. The control group had sham laparotomy only. Three samples of spleen and liver were collected from septic and sham animals at 24 hrs after laparotomy. Changes in expression were measured for 588 annotated mouse genes by using a commercially available complementary DNA microarray kit. MEASUREMENTS AND MAIN RESULTS: Broad-scale gene expression profiles were characterized for septic liver and spleen and compared with sham controls. The analytical tools used included commercially available software packages and a novel analysis program. Very little overlap was observed in the septic gene expression profiles of these two organs. Most of the genes identified have previously been linked to regulation of the inflammatory response; importantly, however, some have not. In addition, hierarchical cluster analysis showed that cecal ligation and puncture at 24 hrs induced coordinate expression of genes that alter cell signaling and survival pathways in spleen, consistent with previously published reports of sepsis-induced splenocyte apoptosis. The current limitations of microarray analysis as reflected in these studies are also discussed. CONCLUSIONS: Microarray technology provides a powerful new tool for rapidly analyzing tissue-specific changes in gene expression induced by sepsis in animal models. To our knowledge, these data constitute the first report on the use of microarrays to determine the sepsis transcriptome.

Animals↗

PubMed2004

Catalase deficiency drastically affects gene expression induced by high light in Arabidopsis thaliana.

In plants, hydrogen peroxide (H(2)O(2)) plays a major signaling role in triggering both a defense response and cell death. Increased cellular H(2)O(2) levels and subsequent redox imbalances are managed at the production and scavenging levels. Because catalases are the major H(2)O(2) scavengers that remove the bulk of cellular H(2)O(2), altering their levels allows in planta modulation of H(2)O(2) concentrations. Reduced peroxisomal catalase activity increased sensitivity toward both ozone and photorespiratory H(2)O(2)-induced cell death in transgenic catalase-deficient Arabidopsis thaliana. These plants were used as a model system to build a comprehensive inventory of transcriptomic variations, which were triggered by photorespiratory H(2)O(2) induced by high-light (HL) irradiance. In addition to an H(2)O(2)-dependent and -independent type of transcriptional response during light stress, microarray analysis on both control and transgenic catalase-deficient plants, exposed to 0, 3, 8, and 23 h of HL, revealed several specific regulatory patterns of gene expression. Thus, photorespiratory H(2)O(2) has a direct impact on transcriptional programs in plants.

Arabidopsis↗

PubMed2026

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n = 4), Leber hereditary optic neuropathy (n = 13), and Wolfram syndrome (n = 5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

Humans↗

PubMed2025

Blood from septic patients with necrotising soft tissue infection treated with hyperbaric oxygen reveal different gene expression patterns compared to standard treatment.

BACKGROUND: Sepsis and shock are common complications of necrotising soft tissue infections (NSTI). Sepsis encompasses different endotypes that are associated with specific immune responses. Hyperbaric oxygen (HBO2) treatment activates the cells oxygen sensing mechanisms that are interlinked with inflammatory pathways. We aimed to identify gene expression patterns associated with effects of HBO2 treatment in patients with sepsis caused by NSTI, and to explore sepsis-NSTI profiles that are more receptive to HBO2 treatment. METHODS: An observational cohort study examining 83 NSTI patients treated with HBO2 in the acute phase of NSTI, fourteen of whom had received two sessions of HBO2 (HBOx2 group), and another ten patients (non-HBO group) who had not been exposed to HBO2. Whole blood RNA sequencing and clinical data were collected at baseline and after the intervention, and at equivalent time points in the non-HBO group. Gene expression profiles were analysed using machine learning techniques to identify sepsis endotypes, treatment response endotypes and clinically relevant transcriptomic signatures of response to treatment. RESULTS: We identified differences in gene expression profiles at follow-up between HBO2-treated patients and patients not treated with HBO2. Moreover, we identified two patient endotypes before and after treatment that represented an immuno-suppressive and an immune-adaptive endotype respectively, and we characterized the genetic profile of the patients that transition from the immuno-suppressive to the immune-adaptive endotype after treatment. We discovered one gene MTCO2P12 that distinguished individuals who altered their endotype in response to treatment from non-responders. CONCLUSION: The global gene expression pattern in blood changed in response to HBO2 treatment in a direction associated with clinical biochemistry improvement, and the study provides potential novel biomarkers and pathways for monitoring HBO2 treatment effects and predicting an HBO2 responsive NSTI-sepsis profile. TRIAL REGISTRATION: Biological material was collected during the INFECT study, registered at ClinicalTrials.gov (NCT01790698) 04/02/2013.

Humans↗

PubMed2003

Transcriptional profiling of ubp10 null mutant reveals altered subtelomeric gene expression and insurgence of oxidative stress response.

UBP10 codes for a deubiquitinating enzyme of Saccharomyces cerevisiae whose loss of function determines slow growth rate and partial impairment of silencing at telomeres and HM loci. A genome-wide analysis performed on a ubp10 disruptant revealed alterations in expression of subtelomeric genes together with a broad change in the whole transcriptional profile, closely parallel to that induced by oxidative stress. This response was accompanied by intracellular accumulation of reactive oxygen species as well as by DNA fragmentation and phosphatidylserine externalization, two markers of apoptosis. SIR4 inactivation mitigated the wide transcriptome remodeling of the ubp10 null mutant affecting particularly the stress transcriptional profile. Moreover, the ubp10sir4 disruptant did not display apoptotic markers. These results argue in favor of an involvement of deubiquitination in transcriptional control and suggest a linkage between oxidative stress and apoptotic pathway in budding yeast.

Apoptosis↗

PubMed2004

Characterization of antirrhinum petal development and identification of target genes of the class B MADS box gene DEFICIENS.

The class B MADS box transcription factors DEFICIENS (DEF) and GLOBOSA (GLO) of Antirrhinum majus together control the organogenesis of petals and stamens. Toward an understanding of how the downstream molecular mechanisms controlled by DEF contribute to petal organogenesis, we conducted expression profiling experiments using macroarrays comprising >11,600 annotated Antirrhinum unigenes. First, four late petal developmental stages were compared with sepals. More than 500 ESTs were identified that comprise a large number of stage-specifically regulated genes and reveal a highly dynamic transcriptional regulation. For identification of DEF target genes that might be directly controlled by DEF, we took advantage of the temperature-sensitive def-101 mutant. To enhance the sensitivity of the profiling experiments, one petal developmental stage was selected, characterized by increased transcriptome changes that reflect the onset of cell elongation processes replacing cell division processes. Upon reduction of the DEF function, 49 upregulated and 52 downregulated petal target genes were recovered. Eight target genes were further characterized in detail by RT-PCR and in situ studies. Expression of genes responding rapidly toward an altered DEF activity is confined to different petal tissues, demonstrating the complexity of the DEF function regulating diverse basic processes throughout petal morphogenesis.

Antirrhinum↗

PubMed2005

Transcriptomic and proteomic patterns of systemic inflammation in on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) provides controlled operative conditions but induces a whole-body inflammatory response capable of initiating devastating morbidity and mortality. Although technically more demanding, deliberate avoidance of CPB in off-pump surgery attenuates the physiological insult associated with CABG. METHODS AND RESULTS: To systematically assess the molecular mechanisms underlying the better-preserved remote organ function, we studied gene expression patterns in leukocytes and plasma proteomic response to on-pump and off-pump CABG. Proteomic analysis confirmed (tumor necrosis factor-alpha, interleukin [IL]-6, IL-10) and expanded (eg, interferon [IFN]-gamma, granulocyte colony-stimulating factor [G-CSF], monocyte chemotactic protein-1, macrophage inflammatory protein-1beta) the mediators released on CPB, whereas blood leukocyte transcriptomics suggested that circulating leukocytes are not primarily responsible for this response. Interestingly, release of some cytokines (eg, IL-6, IFN-gamma, G-CSF) was observed on off-pump surgery to a similar extent but with delayed kinetics. A total of 45 of 4868 transcripts were identified to be significantly altered as a result of initiation of CPB. Systematic analysis of transcriptional activation by CPB revealed primarily genes involved in inflammation-related cell-cell communication (such as L-selectin or intercellular adhesion molecule-2) and signaling (such as IL-1, IL-8, or IL-18 receptors and toll-like receptors 4, 5, and 6), thus confirming a "primed" phenotype of circulating peripheral blood mononuclear cells. CONCLUSIONS: Gene array and multiplex protein analysis, only in concert, can illuminate the molecular mechanisms responsible for systemic sequelae of CPB and indicate that circulating leukocytes overexpress adhesion and signaling factors after contact with CPB, which potentially facilitates their trapping, eg, in the lungs and may promote a subsequent tissue-associated inflammatory response.

Animals↗

PubMed2005

Global gene repression in hepatocellular carcinoma and fetal liver, and suppression of dudulin-2 mRNA as a possible marker for the cirrhosis-to-tumor transition.

BACKGROUND/AIMS: Whether the transcriptional reprogramming process induced by hepatocellular carcinoma recapitulates that of the developing liver is at present unclear. METHODS: With a complete coverage of the liver transcriptome by microarray using adult livers as controls, we searched for similarities and differences in mRNA abundances between hepatocellular carcinoma nodules and fetal livers taken before (early) or after (late) the 22-24th week of gestation. Changes in some mRNA levels were studied in further liver samples by quantitative RT-PCR. RESULTS: Altered gene expression in hepatocellular carcinoma mostly results in down-regulated mRNAs which largely overlap with those repressed in the late fetal liver. Different frequencies of transcription factor binding sites in the down-regulated genes vs control genes as well as changes in abundance of mRNAs for relevant transcription factors point to a transcriptional repression. The down-regulated mRNAs code for proteins involved in (i) transcription and translation, (ii) specific functions of the differentiated hepatocyte or (iii) activation of proliferation and apoptosis. CONCLUSIONS: Apoptosis limitation is likely to predominate over active proliferation during liver development and hepatocellular carcinoma. Repression of the apoptosis-associated dudulin-2 mRNA points to a potential marker for the transition from a carcinoma-free to carcinoma-associated cirrhosis.

Aged↗

PubMed2025

Tonoplast sucrose transporter SUT4-dependent sugar partitioning modulates phenological transitions and reproductive success in poplar.

Climate uncertainty is intensifying the need for greater plasticity in carbohydrate reserve utilization to support winter survival and spring growth in woody perennials. In poplar, the single-copy SUT4, which encodes a tonoplast-localized sucrose transporter, and the SUT5/SUT6 genome duplicates, which encode plasma membrane-localized transporters, are expressed year-round, with SUT4 showing the highest expression during cool seasons. Given its role in vacuolar sucrose efflux and winter-predominant expression, SUT4 may play a key role in modulating seasonal carbohydrate dynamics. While SUT4-knockdown and knockout effects have been studied under greenhouse conditions, their impact under field conditions remains unexplored. Here, we report a field-based study comparing CRISPR knockout mutants of winter-expressed SUT4 and SUT5/SUT6 in Populus tremula × alba. We show that sut4, but not sut5/6, mutants exhibited earlier autumn leaf senescence, delayed spring bud flush, reduced stem growth, and altered sugar partitioning in winter xylem and bark relative to controls. After 2 years in the field, all genotypes flowered before leaf flush in early spring; however, sut4 mutants produced sterile ovules despite developing normal-looking catkins. Metabolic profiling revealed disrupted sucrose and raffinose dynamics in elongating sut4 catkins. This was accompanied by transcriptomic signatures of elevated stress and downregulation of proanthocyanidin biosynthesis and circadian clock genes. These findings highlight the critical role of SUT4 in coordinating sugar allocation, stress responses, and seasonal development in poplar.

Populus↗

PubMed2005

Antisense transcription in the mammalian transcriptome.

Antisense transcription (transcription from the opposite strand to a protein-coding or sense strand) has been ascribed roles in gene regulation involving degradation of the corresponding sense transcripts (RNA interference), as well as gene silencing at the chromatin level. Global transcriptome analysis provides evidence that a large proportion of the genome can produce transcripts from both strands, and that antisense transcripts commonly link neighboring "genes" in complex loci into chains of linked transcriptional units. Expression profiling reveals frequent concordant regulation of sense/antisense pairs. We present experimental evidence that perturbation of an antisense RNA can alter the expression of sense messenger RNAs, suggesting that antisense transcription contributes to control of transcriptional outputs in mammals.

Animals↗

PubMed2026

DNA methylation as a driver of lung fibroblast senescence in COPD.

Cellular senescence is increasingly recognized as a hallmark of chronic obstructive pulmonary disease (COPD), with higher levels in lung fibroblasts from COPD patients. Upon senescence, both hypomethylation and hypermethylation have been described but not in COPD-derived fibroblasts yet. This study investigated whether altered DNA methylation can be a driver of fibroblast senescence in COPD. Genome-wide gene expression and DNA methylation data were generated from primary lung fibroblasts of 11 COPD stage IV patients and 10 matched controls. Gene expression of six well-known senescence genes was compared between COPD and control. COPD-associated senescence genes were correlated with their related CpG sites in an expression quantitative trait methylation (eQTM) analysis. Methylation levels of significant eQTMs were compared between COPD and control fibroblasts. A causal relationship between altered DNA methylation and senescence was validated in 5-Aza-2'-deoxycytidine (5-Aza-2'-dC)-treated primary lung fibroblasts. Gene expression of CDKN1A, CDKN2A, and CDKN2B was higher, while LMNB1 expression was lower in COPD-derived fibroblasts compared to controls. A total of 19 eQTMs were found for the COPD-associated senescence genes CDKN1A (9), CDKN2A (1), and LMNB1 (9). Among these, seven CpG sites (4 for CDKN1A and 3 for LMNB1) exhibited differential methylation between COPD and control. Treatment with 5-Aza-2'-dC led to global demethylation and increased senescence and, importantly, confirmed the association between senescence and hypomethylation of the COPD-associated CpG site cg04924375. Altered DNA methylation is linked to fibroblast senescence in COPD, and seven CpG sites are identified as potential epigenetic regulators of the senescence genes CDKN1A and LMNB1.NEW & NOTEWORTHY This study identifies DNA methylation as a mechanistic contributor to lung fibroblast senescence in chronic obstructive pulmonary disease (COPD). By integrating DNA methylation data with the transcriptomic data of senescence-related genes, we uncovered seven COPD-associated CpG sites linked to the senescence regulators CDKN1A and LMNB1. Pharmacological demethylation induces fibroblast senescence and is consistent with a functional role for hypomethylation at cg04924375, providing new insight into epigenetic regulation of cellular senescence in COPD lung fibroblasts.

Humans↗

PubMed2003

Gene expression phenotypes of Arabidopsis associated with sensitivity to low temperatures.

Chilling is a common abiotic stress that leads to economic losses in agriculture. By comparing the transcriptome of Arabidopsis under normal (22 degrees C) and chilling (13 degrees C) conditions, we have surveyed the molecular responses of a chilling-resistant plant to acclimate to a moderate reduction in temperature. The mRNA accumulation of approximately 20% of the approximately 8,000 genes analyzed was affected by chilling. In particular, a highly significant number of genes involved in protein biosynthesis displayed an increase in transcript abundance. We have analyzed the molecular phenotypes of 12 chilling-sensitive mutants exposed to 13 degrees C before any visible phenotype could be detected. The number and pattern of expression of chilling-responsive genes in the mutants were consistent with their final degree of chilling injury. The mRNA accumulation profiles for the chilling-lethal mutants chs1, chs2, and chs3 were highly similar and included extensive chilling-induced and mutant-specific alterations in gene expression. The expression pattern of the mutants upon chilling suggests that the normal function of the mutated loci prevents a damaging widespread effect of chilling on transcriptional regulation. In addition, we have identified 634 chilling-responsive genes with aberrant expression in all of the chilling-lethal mutants. This reference gene list, including genes related to lipid metabolism, chloroplast function, carbohydrate metabolism and free radical detoxification, represents a potential source for genes with a critical role in plant acclimation to suboptimal temperatures. The comparison of transcriptome profiles after transfer of Arabidopsis plants from 22 degrees C to 13 degrees C versus transfer to 4 degrees C suggests that quantitative and temporal differences exist between these molecular responses.

Acclimatization↗

PubMed2025

Multi-Omics Platforms Reveal Synergistic Intestinal Toxicity in Tilapia from Acute Co-Exposure to Polystyrene Microplastics, Sulfamethoxazole, and BDE153.

Polystyrene microplastic (MP) and its co-existing contaminants may exert different toxic effects on its surrounding aquatic organisms. In order to detect the intestinal harmful responses, tilapia were subjected to exposure with 75 nm of MPs, 100 ng·L-1 of sulfamethoxazole (SMZ), 5 ng·L-1 of BDE153, and combinations thereof over periods of 2, 4, and 8 days. Enzymatic assays, transcriptomics, proteomics, and metabolomics were employed to evaluate intestinal histopathological effects. Results showed that significant reductions were observed in ATP, ROS, SOD, EROD, lipid metabolism-related enzymes, pro-inflammatory cytokines (TNFα and IL-1β), and apoptosis marker caspase 3 across all groups at day 8. Histological evaluation revealed diminished goblet cell density, with distinct vacuole formation in the BDE153+MPs group. KEGG pathway analysis highlighted disruptions in endocytosis, MAPK signaling, phagosome formation, and actin cytoskeleton regulation. Proteomic findings indicated notable enrichment in endocytosis (decreased sorting nexin-2; increased Si:dkey-13a21.4), MAPK/PPAR signaling, protein processing in the endoplasmic reticulum (Sec61 subunit gamma), and cytoskeletal modulation (reduced fibronectin; elevated activation peptide fragment 1), with or without SMZ and BDE153. Metabolomic profiling showed significant alterations in ABC transporters, aminoacyl-tRNA biosynthesis, protein digestion and absorption, and linoleic acid metabolism. In summary, these findings suggest that BDE153 and MPs synergistically exacerbate intestinal damage and gene/protein expression over time, while SMZ appears to exert an antagonistic, mitigating effect.

Animals↗

PubMed2026

Loss of PBRM1 accelerates pancreatic cancer progression by inducing acquisition of mesenchymal phenotype and inflammatory cancer-associated fibroblasts reprogramming.

BACKGROUND: PBRM1 is an important subunit of the SWI/SNF complex, which broadly regulates gene transcription by chromatin remodeling. Genomic alterations of PBRM1 have been found in patients with pancreatic ductal adenocarcinoma (PDAC), but its molecular functions remain unclear. METHODS: Clinical relevance of PBRM1 was analyzed by using human PDAC samples and public genomic datasets. Mice with concomitant pancreas-specific Pbrm1 deletion in Kras-driven genetic PDAC models were generated. Single-cell transcriptomics were performed to determine tumor phenotype and microenvironment reprogramming. RESULTS: Reduction of PBRM1 expression was observed in human PDAC tissues and correlated with poor prognosis and metastasis. Pbrm1 loss promoted ductal metaplasia and delayed epithelial recovery in mice with caerulein-induced pancreatic injury. In PDAC model with either mutant Kras alone or in combination with Trp53 mutation, lack of Pbrm1 markedly accelerated tumor development and progression. Bulk transcriptomics and scRNA-seq identified reprogramming of both tumor compartment with mesenchymal phenotype acquisition and stroma compartment with inflammatory cancer-associated fibroblasts (iCAFs) transformation. Mechanistically, Pbrm1 deletion induced Zeb1 upregulation through epigenetic chromatin remodeling, thereby enhancing epithelial-mesenchymal and basal-like subtype transition. CONCLUSIONS: These findings indicated a tumor-suppressing role of PBRM1 in PDAC. PBRM1-deficient PDAC constitutes a specific subgroup of patients with aggressive phenotype and prognostic significance.

Animals↗