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PubMed2026

Integrated transcriptomic and metabolomic analyses provide new insights into the response of black rockfish (Sebastes schlegelii) larvae to temperature fluctuations.

Sebastes schlegelii usually encounter elevated and fluctuating water temperatures near its upper thermal limit in summer, yet the hepatic responses of larvae to repeated temperature fluctuation regimes remain unclear. To address this question, S. schlegelii larvae were exposed for 8 days to four thermal regimes: constant 18 °C (CT), constant 28 °C (HT), intermittent cooling from 18 to 8 °C followed by recovery to 18 °C (FL), and intermittent warming from 18 to 28 °C followed by recovery to 18 °C (FH). Survival rate was evaluated, and integrated liver transcriptomic and metabolomic analyses were performed. Final survival rates were 96.67% in the CT group, 97.78% in the FL group, and 77.78% in the FH group. Survival rate in the HT group (38.89%) was significantly lower than that in the other three groups (P < 0.05). HTvsCT, FLvsCT, FHvsCT, and FHvsHT comparisons identified 2598, 1207, 622, and 2404 differentially expressed genes and 627, 606, 690, and 610 differential metabolites, respectively. KEGG enrichment analyses of DEGs and SDMs in HTvsCT highlighted HSP-mediated proteostasis, endoplasmic-reticulum protein processing, branched-chain and sulfur amino acid metabolism, glutathione metabolism, and central carbon metabolism, with upregulated hsp90aa1, bckdha, gclc, and pfkp and reduced levels of branched-chain amino acids and methionine. Compared with HT, FH showed attenuated disturbances in proteostasis, amino acid and redox regulation, and central carbon metabolism, together with recovery-associated glycerophospholipid turnover. FL primarily induced polyunsaturated fatty acid (PUFA)-related membrane lipid remodeling. These findings indicate that hepatic responses differed between continuous high-temperature exposure and temperature fluctuations and between fluctuation regimes.

Animals↗

PubMed2026

Transcriptomic and RNAi analyses reveal chloride channel 3-associated osmoregulation in Litopenaeus vannamei under low-salinity stress.

Chloride channels and transporters are important for cellular volume regulation and salinity adaptation in euryhaline crustaceans, yet the intestinal transcriptional relationship between plasma-membrane and intracellular chloride pathways remains unclear in Litopenaeus vannamei. In this study, RNA interference of anoctamin 1 (ANO1) was combined with intestinal transcriptome sequencing under the production-relevant low-salinity condition of salinity 3. ANO1 silencing produced a focused transcriptional response, with 16 differentially expressed genes (DEGs) identified (11 upregulated and 5 downregulated). Functional enrichment indicated that these genes were associated with transporter activity, cytoskeletal organization, extracellular matrix-receptor interaction, membrane lipid metabolism, and vesicular processes. Notably, a transcript encoding chloride channel protein 3 (CLC-3) was significantly upregulated following ANO1 knockdown, suggesting a potential transcriptional relationship between ANO1 and CLC-3 in chloride homeostasis. Based on this finding, CLC-3 was selected for full-length cDNA cloning, sequence characterization, salinity-gradient expression analysis, and RNAi-based functional assessment. The cloned CLC-3 cDNA was 2883 bp in length and encoded an 850 amino acid protein containing a conserved voltage-gated chloride channel (Voltage-CLC) domain and two cystathionine β-synthase domains. Phylogenetic analysis placed LvCLC-3 within the intracellular CLC-c clade, and tissue distribution analysis showed the highest CLC-3 expression in the intestine. Intestinal CLC-3 expression responded nonlinearly to salinity variation, peaking at salinity 20. Under salinity 3, CLC-3 knockdown reduced ANO1, Na+/K+-ATPase alpha subunit, and Na+-K+-2Cl- cotransporter transcript levels, whereas glutamate-gated chloride channel expression increased. Mild hepatopancreatic structural alterations were also observed after CLC-3 knockdown. These findings suggest that CLC-3 is a salinity-responsive intracellular chloride-transporter candidate associated with intestinal ion-transport-related transcriptional responses after ANO1 suppression in L. vannamei, although the underlying physiological mechanism requires further validation.

Animals↗

PubMed2025

Combined somatic mutation and transcriptome analysis reveals region-specific differences in clonal architecture in human cortex.

The human cerebral cortex is specialized into regions, but little is known about how human cellular lineages shape cortical regional variation and neuronal cell-type distribution during development. Here, we map single-cell lineages of human cortical regions and neuronal subtypes using >1,000 somatic single-nucleotide variants (sSNVs) identified from deep bulk whole-genome sequencing and analyzed over 25 regions and >72,000 single cells. In the fronto-parietal cortex, sSNVs are rarely restricted, marking neuron-generating clones that disperse into neighboring regions. In contrast, the primary visual cortex harbors 30%-70% more sSNVs than the neighboring secondary visual cortex. Clones at this border exhibit more restricted dispersion, suggesting late developmental lineage segregation. Single-nucleus sSNV and whole-transcriptome analysis reveal glutamatergic neuron clones with modest regional restrictions that share low-mosaic sSNVs with some GABAergic neurons, suggesting a recent dorsal cortical progenitor. Our analysis reveals human-specific cortical lineage patterns, regional differences in clonal patterns, and late divergence of some glutamatergic/GABAergic lineages.

Humans↗

PubMed2025

Colorectal Liver Metastasis Pathomics Model: Integrating Single-Cell and Spatial Transcriptome Analysis With Pathomics for Predicting Liver Metastasis in Colorectal Cancer.

The liver is the primary target organ for hematologic metastasis of colorectal cancer (CRC), and CRC liver metastasis (CRLM) often precludes radical resection, making it the leading cause of death in patients with CRC. To improve the identification and prediction of liver metastasis risk, we identified a cell type of liver metastasis--triggering malignant cells (LMTMCs) through integrating single-cell RNA sequencing and spatial transcriptome analysis. Multiomics cell communication analysis indicated that the interaction between fibroblasts and LMTMCs through the COL1A1-CD44/SDC4 and LAMA4-CD44 signaling axes could promote CRLM. By applying the one-class logistic regression algorithm, we developed a CRLM scoring system in the bulk RNA-sequencing data according to the abundance of LMTMCs in each individual. Using the grouping labels derived from the CRLM scoring system in the bulk data and the corresponding whole-slide images without any manual annotations at the region or pixel level, processed via slide-level weakly supervised learning, a deep-learning model based on the ResNet18 architecture, called Colorectal Liver Metastasis Pathomics Model, was developed to predict the risk of liver metastasis in patients with CRC. The Colorectal Liver Metastasis Pathomics Model achieved an area under the curve of 0.84 at the internal test set of The Cancer Genome Atlas-CRC histology images. In the external independent validation sets, namely the Affiliated Hospital of Southwest Medical University and the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University cohorts, the areas under the curve were 0.89 and 0.72, respectively, indicating effective classification performances. This study provided new insights and tools for the early identification of CRLM and demonstrated the potential of combining multiomics with deep learning-based pathomics in cancer research.

Humans↗

PubMed2025

An Integrated Clinical Genomic and Transcriptomic Subgrouping of Central Chondrosarcoma.

Central conventional chondrosarcoma, a malignant cartilage-producing bone tumor, is the second most common bone sarcoma. Chondrosarcomas are histologically graded, which is so far the best predictor of survival. Early mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are frequent, leading to the production of the oncometabolite D-2-hydroxyglutarate, which affects DNA methylation, resulting in a preferred chondrogenic differentiation over osteogenic differentiation of mesenchymal stem cells, which are currently considered the precursor cells of chondrosarcoma. DNA methylation profiling has previously revealed distinct profiles between IDH-mutant and IDH-wild-type chondrosarcomas, but the presence of further DNA methylation subgroups indicates that classification based solely on IDH status is too simplistic. In this study, we aim to identify biological subgroups in a total of 116 chondrosarcomas by integrating clinical data, IDH mutation status, gene expression, and genome-wide loss of heterozygosity (LOH). Clinical associations were observed between several factors, including sex and histological grade, as well as tumor site and IDH mutation status. RNA sequencing and genome-wide LOH confirmed the distinction between IDH-wild-type and IDH-mutant chondrosarcomas, where the number of chromosome arms affected by LOH was significantly higher in IDH-wild-type tumors than in IDH-mutant tumors. However, no clear subgroups emerged within each IDH group. Further clustering on RNA expression of differentiation markers identified subgroups characterized by chondrogenic, osteogenic, resting chondrocyte, or dedifferentiated profiles. These different subgroups showed a specific clinical presentation and suggest different precursor cells. Instead of a simple dichotomy between IDH-mutant and IDH-wild-type, our integrated approach highlights interconnected clinical, genomic, and transcriptomic patterns that offer a more nuanced view of chondrosarcoma biology and might potentially guide treatment stratification.

Humans↗

PubMed2025

CRISPR tools for T cells: targeting the genome, epigenome, and transcriptome.

T cell therapy has curative potential for many cancers. Despite impressive clinical efficacy in hematological malignancies, current T cell therapy still faces challenges related to sustaining responses, antigen escape, cytotoxicity, limited accessibility, and difficulties in treating solid tumors. The advent of CRISPR (clustered regularly interspaced short palindromic repeats) technologies provides a promising solution to these challenges. CRISPR technologies have grown from merely tools for gene knockout to sophisticated tools that can engineer cells at various levels of the genome, epigenome, and transcriptome. In this review we discuss recent technological advancements and how their application to T cells has the potential to steer the next generation of cellular therapy. We highlight emerging applications and current technological limitations that future tool development aims to overcome.

Humans↗

PubMed2025

Deciphering estrogen receptor alpha-driven transcription in human endometrial stromal cells via transcriptome, cistrome, and integration with chromatin landscape.

OBJECTIVE: To investigate estrogen receptor gene 1 (ESR1) and estrogen-driven transcription in human endometrial stromal cells. DESIGN: RNA sequencing (RNA-seq) and Cleavage Under Targets and Release Using Nuclease (Cut&Run) were performed on telomerase-immortalized human endometrial stromal cells with Clustered Regularly Interspaced Short Palindromic Repeats-mediated ESR1 activation. Hi-C-based chromatin architecture analysis (H3K27ac HiChIP) was conducted in primary endometrial stromal cells. SUBJECTS: Biopsies from two healthy, reproductive-aged volunteers with regular menstrual cycles and no history of gynecological malignancies. EXPOSURE: The ESR1-activated and control endometrial stromal cells were treated with estradiol (E2) or vehicle. Primary endometrial stromal cells were treated with vehicle or a decidualization cocktail. MAIN OUTCOME MEASURES: Differential gene expression analysis (RNA-seq) identified ligand-independent and -dependent ESR1 activity. Cut&Run profiled ESR1 genomic binding in ESR1-activated cells. H3K27ac HiChIP mapped hormone-induced changes in chromatin looping in primary cells. RESULTS: Among seven tested guide RNAs (gRNA), the ESR1-3 gRNA induced robust ESR1 activation and restored E2 responsiveness. Bulk RNA-seq revealed both ligand-dependent and -independent ESR1 transcriptional programs regulating inflammation, proliferation, and cancer-related pathways. Notably, 72% of differentially expressed genes overlapped with genes active in human endometrial tissue during the proliferative estrogen-dominant phase, supporting their physiological relevance. The Cut&Run-seq identified genome-wide ESR1 binding sites, with most binding sites located at distal regulatory elements. Integration of Cut&Run data with H3K27ac HiChIP chromatin loops linked distal ESR1 binding sites to gene promoters, including genes involved in decidualization (e.g., FOXO1) and endometrial cancer (e.g., ERRFI1, NRIP1, and EPAS1). Functional assays showed that ESR1 promotes cell viability and, in the presence of E2, enhances migration. CONCLUSION: The CRISPR-mediated ESR1 activation restores estrogen responsiveness in endometrial stromal cells. Combined transcriptomic, cistromic, and chromatin architecture analyses reveal ESR1's role in regulating decidualization and inflammation-related gene networks, with relevance to endometrial pathologies including endometrial cancer. This model serves as a powerful tool to study estrogen signaling in endometrial stromal cell biology and related pathologies.

Humans↗

PubMed2024

Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures.

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.

Animals↗

PubMed2026

Integrating transcriptomics and metabolomics reveals the molecular landscape of sperm maturation driven by regional differentiation in the epididymis of Guizhou-Guiqian semi-fine wool sheep.

Epididymal regionalized differentiation is crucial for sperm maturation. However, little is known about the synergistic remodeling mechanisms of different epididymal segments at the transcriptional and metabolic levels during sexual maturation in ruminants (especially sheep). We investigated the caput, corpus, and cauda epididymidis of pre-pubertal (2-month-old) and post-pubertal (7-month-old) Guizhou-Guiqian semi-fine wool sheep using histology, RNA sequencing, and metabolomics. Post-pubertal tissues exhibited increased luminal diameters, cilia lengths, and abundant cauda spermatozoa. Transcriptomic analysis revealed increasing differentially expressed genes (DEGs) along the caput-corpus-cauda axis (4642, 6103, and 7698 DEGs, respectively). Metabolomics detected 786 unique differentially accumulated metabolites (DAMs). Region-specific analysis showed that in the caput, up-regulated pathways (fructose/mannose metabolism; HK2, ALDOA, HKDC1) provide energy and substrates for initial sperm motility. In the corpus, down-regulated genes associated with extracellular matrix and tight junctions suggested epithelial barrier remodeling to establish an immune-tolerant microenvironment. The cauda specifically up-regulated the pentose phosphate pathway (FBP1, GPI) and glutathione metabolism, maintaining redox homeostasis for long-term sperm storage. Additionally, glycerophospholipid metabolism was enriched across all segments, where PEMT, AGPAT5, and LCAT likely regulate sperm plasma membrane fluidity. In conclusion, during sexual maturation, the caput drives energy metabolism and glycosylation, the corpus establishes immune tolerance, and the cauda maintains antioxidant homeostasis. The glycerophospholipid network throughout the across all epididymal segments synergistically remodels sperm membrane. This study reveals the underlying multi-omics regulatory mechanisms of epididymal functional differentiation, providing a theoretical basis for elucidating the molecular mechanisms of sperm maturation in this breed and for the molecular breeding of early reproductive performance in rams.

Animals↗

PubMed2024

Haplotype-resolved genome assembly and implementation of VitExpress, an open interactive transcriptomic platform for grapevine.

Haplotype-resolved genome assemblies were produced for Chasselas and Ugni Blanc, two heterozygous Vitis vinifera cultivars by combining high-fidelity long-read sequencing and high-throughput chromosome conformation capture (Hi-C). The telomere-to-telomere full coverage of the chromosomes allowed us to assemble separately the two haplo-genomes of both cultivars and revealed structural variations between the two haplotypes of a given cultivar. The deletions/insertions, inversions, translocations, and duplications provide insight into the evolutionary history and parental relationship among grape varieties. Integration of de novo single long-read sequencing of full-length transcript isoforms (Iso-Seq) yielded a highly improved genome annotation. Given its higher contiguity, and the robustness of the IsoSeq-based annotation, the Chasselas assembly meets the standard to become the annotated reference genome for V. vinifera. Building on these resources, we developed VitExpress, an open interactive transcriptomic platform, that provides a genome browser and integrated web tools for expression profiling, and a set of statistical tools (StatTools) for the identification of highly correlated genes. Implementation of the correlation finder tool for MybA1, a major regulator of the anthocyanin pathway, identified candidate genes associated with anthocyanin metabolism, whose expression patterns were experimentally validated as discriminating between black and white grapes. These resources and innovative tools for mining genome-related data are anticipated to foster advances in several areas of grapevine research.

Vitis↗

PubMed2025

Learning directed acyclic graphs for ligands and receptors based on spatially resolved transcriptomic data of ovarian cancer.

To unravel the mechanism of immune activation and suppression within tumors, a critical step is to identify transcriptional signals governing cell-cell communication between tumor and immune/stromal cells in the tumor microenvironment. Central to this communication are interactions between secreted ligands and cell-surface receptors, creating a highly connected signaling network among cells. Recent advancements in in situ-omics profiling, particularly spatial transcriptomic (ST) technology, provide unique opportunities to directly characterize ligand-receptor signaling networks that power cell-cell communication. In this paper, we propose a novel statistical method, LRnetST, to characterize the ligand-receptor interaction networks between adjacent tumor and immune/stroma cells based on ST data. LRnetST utilizes a directed acyclic graph model with a novel approach to handle the zero-inflated distributions of ST data. It also leverages existing ligand-receptor regulation databases as prior information, and employs a bootstrap aggregation strategy to achieve robust network estimation. Application of LRnetST to ST data of high-grade serous ovarian tumor samples revealed both common and distinct ligand-receptor regulations across different tumors. Some of these interactions were validated through both a MERFISH dataset and a CosMx SMI dataset of independent ovarian tumor samples. These results cast light on biological processes relating to the communication between tumor and immune/stromal cells in ovarian tumors. An open-source R package of LRnetST is available on GitHub at https://github.com/jie108/LRnetST.

Humans↗

PubMed2026

Transcriptomic and Metabolomic Profiling Identifies a Core Gene-Metabolite Axis Driving African Swine Fever Virus Replication in the Soft Tick Ornithodoros lahorensis.

African swine fever virus (ASFV) causes an incurable swine disease with nearly 100% mortality, posing a catastrophic threat to global pig production. The soft tick Ornithodoros lahorensis acts as a critical biological vector that sustains persistent ASFV replication and mediates long-distance viral transmission, yet the molecular mechanisms governing ASFV-tick interplay remain poorly understood. Here, we integrated transcriptomics and metabolomics to systematically dissect molecular changes in O. lahorensis across three infection stages: Uninfected control, early infection (7 days post-infection, dpi), and late persistent infection (21 dpi). Multi-omics integration revealed that ASFV extensively remodels tick host metabolism, predominantly activating purine/pyrimidine metabolism, lipid biosynthesis, and energy metabolism. We further characterized a conserved regulatory module consisting of 12 core genes and 8 signature metabolites that collectively support ASFV genome replication and virion assembly. Three hub metabolic genes (TK1, ATP5F1B, and IMPDH) were selected for functional validation via siRNA silencing in ticks; individual gene silencing suppressed ASFV loads by 89.2%, 91.5%, and 87.8%, respectively (p < 0.001***). This work represents the first comprehensive multi-omics investigation of ASFV infection in O. lahorensis. We identified tick-specific molecular targets to block vector-mediated ASFV spread and established a standardized multi-omics analytical pipeline for tick-virus interaction research. Our findings elucidate the mechanistic basis of long-term ASFV persistence in soft ticks and deliver novel actionable clues for developing vector-targeted ASF intervention strategies.

Animals↗

PubMed2025

Genomic and transcriptomic insights into the virulence and adaptation of shock syndrome-causing Streptococcus anginosus.

Streptococcus anginosus is a common isolate of the oral cavity and an opportunistic pathogen for systemic infections. Although the pyogenic infections caused by S. anginosus are similar to those caused by Streptococcus pyogenes, S. anginosus lacks most of the well-characterized virulence factors of S. pyogenes. To investigate the pathogenicity of S. anginosus, we analysed the genome of a newly identified S. anginosus strain, KH1, which was associated with toxic shock-like syndrome in an immunocompetent adolescent. The genome of KH1 contains nine genomic islands, two Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated systems and many phage-related proteins, indicating that the genome is influenced by prophages and horizontal gene transfer. Comparative genome analysis of 355 S. anginosus strains revealed a significant difference between the sizes of the pan genome and core genome, reflecting notable strain variations. We further analysed the transcriptomes of KH1 under conditions mimicking either the oral cavity or the bloodstream. We found that in an artificial saliva medium, the expression of a putative quorum quenching system and pyruvate oxidase for H2O2 production was upregulated, which could optimize the competitiveness of S. anginosus in the oral ecosystem. Conversely, in a modified serum medium, purine and glucan biosynthesis, competence and bacteriocin production were significantly upregulated, likely facilitating the survival of KH1 in the bloodstream. These findings indicate that S. anginosus can utilize diverse mechanisms to adapt to different environmental niches and establish infection, despite its lack of toxin production.

Streptococcus anginosus↗

PubMed2025

Comparative transcriptomics uncovers poplar and fungal genetic determinants of ectomycorrhizal compatibility.

Ectomycorrhizal symbiosis supports tree growth and is crucial for nutrient cycling and temperate and boreal ecosystems functioning. The establishment of functional ectomycorrhiza (ECM) first requires the association of compatible partners. However, host and fungal genetic determinants governing mycorrhizal compatibility are unknown. To identify such factors in poplar and its fungal associates, we mined existing and de novo tree and fungal transcriptional datasets. We identified co-expressed genes enabling ECM symbiosis at early and mature stages of the interaction. These sets of genes can be divided into general fungal-sensing and ECM-specific components. We highlight the importance of fungal modulation of plant JA-related defenses and the regulation of secretory pathways for ECM compatibility, including upregulation of key fungal small secreted proteins, the downregulation of plant secreted peroxidases, and the downregulation of plant cell wall remodeling proteins concomitantly with the upregulation of fungal glycosyl hydrolases acting on pectin. Not only gene regulation, but also its temporal scale and dynamics seem to play a crucial role for mycorrhizal compatibility. The expression profile of the host Common Symbiosis Pathway and nutrient transporters was also studied, revealing constitutive levels of expression and moderate upregulation in compatible ECM interactions. Overall, these results underscore the importance of novel biological functions during the establishment of ECM symbiosis, help us gain insights into the molecular events determining mycorrhiza compatibility, and serve as a data-rich transcriptomic resource to open new research questions in the field.

Mycorrhizae↗

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↗

PubMed2025

Comprehensive analysis of DNA methylome and transcriptome reveals the epigenetic regulation of nitric oxide treatment in delaying apricot fruit senescence.

Apricot produces climacteric fruit, which are perishable after harvest. To elucidate the regulatory role of NO treatment through DNA methylation in post-harvest senescence, apricot fruits were treated with 0.2 mmol/L sodium nitroprusside (SNP) solution for 10 min, with distilled water treatment serving as the control. Treated fruits were then stored at 25°C and 80% relative humidity. Changes in appearance quality, physiological parameters, metabolome profiles, transcriptome dynamics, and DNA methylation patterns were analyzed before and after storage. Results showed that NO treatment delayed apricot softening, increased flavonoid metabolite accumulation, and reduced lipid and abscisic acid accumulation, with these effects correlated to the expression of specific genes and transcription factors. This work reveals the epigenetic regulatory mechanism underlying NO treatment delaying ripening and senescence. Further analysis revealed that the transcription levels of ACO, PAL, UFGT-like, NCED1, PP2C, MYB21, CCoAOMT-like, CYP707A, and ZNF7-like were all correlated with DNA methylation. This indicates that SNP treatment can lead to large changes in DNA methylation levels in apricot fruits, and that the differences in gene transcription levels are associated with the occurrence of hypomethylation and hypermethylation. Collectively, these findings establish an epigenetic framework for post-harvest regulation of apricot fruit, revealing DNA methylation-mediated freshness preservation mechanisms.

DNA Methylation↗

PubMed2024

Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK.

Pseudorabies virus (PRV) is an ideal model for mechanistic investigations into α-herpesvirus. The neurotropism and latent infection of PRV have been extensively studied. Apart from neurological symptoms, diarrhea caused by PRV infection is also an essential cause of mortality in newborn and weaned piglets. However, little research has been done on PRV invasion of the gut. To fill this gap, a nasal drip PRV-infection mouse model was developed, consisting of three groups: the challenged group (Group A), the immunization-challenged group (Group B), and a mock group (Group C). The results showed that immunization with PRV XJ delgE/gI/TK successfully prevented intestinal damage caused by PRV drop-nose infection. Subsequently, intestines were collected for transcriptional analysis. Differentially expressed genes analysis revealed that PRV XJ delgE/gI/TK was effective in reducing the organismal intestinal transcriptional activity caused by PRV. The Group A vs Group C and Group A vs Group B had similar Kyoto Encyclopedia of Genes and Genomes (KEGG)-enriched signaling pathways and the differentially expressed genes were primarily enriched in pathways, such as cell adhesion molecules, focal adhesion kinase, and actin cytoskeleton regulation. Notably, transcriptome analysis indicated that genes associated with the focal adhesion kinase (FAK) signaling pathway (ECM-ITGA/ITGB-p-FAK) were significantly more highly expressed in Group A than in Group B and Group C. The results of quantitative real-time PCR (RT-qPCR) and western blotting were consistent with KEGG analysis. Therefore, we hypothesized that PRV promotes self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway and that PRV XJ delgE/gI/TK immunization could attenuate the intestinal damage caused by PRV by inhibiting the activation of this pathway.IMPORTANCEPseudorabies virus (PRV) poses a significant threat to the swine industry and public health due to its ability to infect multiple species, including humans, leading to substantial economic losses and potential health risks. This study addresses a critical gap in understanding the impact of PRV infection on the gut, which has been less explored compared to its neurological effects. By developing a drip-nose PRV-infection mouse model, the research indicated that PRV might promote self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway, and PRV XJ delgE/gI/TK immunization effectively prevents intestinal damage by significantly reducing the expression of genes in the ECM-ITGA/ITGB-p-FAK signaling pathway. The research has important implications for the swine industry and public health by contributing to the development of better vaccines and treatments, ultimately helping to control PRV and prevent its cross-species transmission.

Animals↗

PubMed2026

Benchmarking urinary cell transcriptomes for noninvasive differentiation of BK polyomavirus-associated nephropathy from T cell-mediated rejection.

BK polyomavirus-associated nephropathy (BKVN) adversely impacts kidney allograft survival and often mimics acute T cell-mediated rejection (TCMR), confounding diagnosis and management. To address this conundrum, we performed unbiased RNA sequencing of urinary cells matched to biopsies classified as BKVN with intragraft inflammation (BKVN-P), BKVN without inflammation (BKVN-N), TCMR, or no rejection (NR). BKVN-N displayed dominant host DNA replication, cell cycle, and repair programs, while BKVN-P samples exhibited expansive innate immune activation, antigen presentation, chemokine upregulation, and epithelial injury. Both BKVN subtypes shared signatures of T cell exhaustion and mature and tolerogenic dendritic cell activation but differed in immune orientation - Th1 predominance in BKVN-N versus Treg and CD8 enrichment in BKVN-P. Compared with TCMR samples, BKVN-P lacked robust TCR/CD28 signaling and was enriched for viral and innate modules; BKVN-N lacked alloimmune activation. B cell exhaustion characterized BKVN-N, while BKVN-P displayed robust B cell activation with metabolic downregulation. A ratiometric urinary cell biomarker, CXCL10 mRNA/CD3E mRNA, distinguished both BKVN subtypes from TCMR with diagnostic accuracy, replicated by quantitative reverse transcription PCR for clinical translation, and confirmed in an independent cohort. These findings demonstrate the utility of urinary cell transcriptomics for resolving viral injury from alloimmunity, enabling precision diagnostics and targeted immunomodulation in kidney transplantation.

Humans↗