Analysis Of Transcriptomic Data Research Articles

Functional analysis of the transcription factor CcUNE10 in red and blue LED light-induced coloration of mandarin fruit.

The peel and flesh of early maturing mandarin fruit in the Chongqing region do not reach maturity at the same time. It was found that red and blue LED light could promote color change in these fruit by inducing the degradation of chlorophyll and the synthesis of carotenoids. Blue LED light was more effective in inducing the synthesis of carotenoids. Analysis of transcriptome data revealed that the transcription factor CcUNE10 (Ciclev10020053mg) may participate in the regulation of mandarin fruit peel coloration under both red and blue LED light. Analysis of the CcUNE10 biological information showed that CcUNE10 is highly homologous to Arabidopsis AtUNE10, and has transcriptionally active elements that are localized in the nucleus and responsive to light, abscisic acid, and growth factors. On the second day following infection, tobacco leaves with heterologous transient overexpression of CcUNE10 showed a significant reduction in chlorophyll b and chlorophyllide b (P < 0.05). Mandarin fruit with transient overexpression of CcUNE10 also showed a significant yellow phenotype on the third day, with a significantly accelerated reduction of chlorophyll and its metabolites (P < 0.05). Significant up-regulation was observed in the genes CcCHlH, CcChlase2, CcNYC1, and CcPAO, which are related to chlorophyll degradation (P < 0.05). In summary, red and blue LED light led to color change in mandarin fruit by inducing chlorophyll degradation and carotenoid synthesis. CcUNE10 may play an important role in red and blue LED irradiation-induced degradation of chlorophyll. © 2025 Society of Chemical Industry.

SLAMF4 orchestrates the cytotoxic response of CD4+ T cells in rheumatoid arthritis.

This study aimed to assess whether signaling lymphocytic activation molecule family receptors (SLAMFs) are involved in the shaping of the pathological response of CD4+ T cells in rheumatoid arthritis (RA). Peripheral blood (PB) and synovial fluid (SF) mononuclear cells from RA patients were freshly isolated. In RA, we used a multi-modal approach to determine the involvement of numerous subpopulations of CD4+ T cells expressing SLAMFs. Experimentally, multiple flow cytometry panels, RNA sequencing and ex vivo stimulations were used. Analyses involved high-dimensional unsupervised clustering of flow cytometry data and pathway enrichment analyses of transcriptomic data. In PB of RA patients with active disease, SLAMF4+ effector memory T cells (Tem) represented the only overrepresented subpopulation of CD4+ T cells expressing SLAMFs. This positive correlation between RA activity and SLAMF4+ Tem was restricted to those co-expressing the intracellular molecule SAP and the tissue-homing receptor CCR5. Gene Set Enrichment Analysis of RNA-sequencing data reveals that SLAMF4+ CCR5+ Tem display a cytotoxicity-related gene signature. Moreover, based on the differential expression of cytotoxicity markers (GPR56, CX3CR1, granzyme-B, perforin and granulysin), unsupervised clustering of flow cytometry data identified distinct subpopulations of PB cytotoxic Tem. Among them, only SLAMF4high SAP+ CCR5+ Tem (Cytotox-F4high Tem) were correlated with RA activity. Remarkably, Cytotox-F4high Tem emerged as the only cytotoxic population of CD4+ T cells (CD4+ CTLs) present in SF of patients with active disease. This study emphasizes that Cytotox-F4high Tem represent a significant CD4+ CTL subpopulation involved in RA, suggesting that their inhibition represent a promising therapeutic interest.

Identification and validation VAT1 in gastric cancer through bioinformatics and experimental analysis.

This study investigated the expression pattern of Vesicular Amine Transporter 1 (VAT1) in gastric cancer (GC) and its impact on prognosis, alongside evaluating its potential as a biomarker for immunotherapy and chemotherapy. Analysis of transcriptomic data, supported by experimental validation, revealed that VAT1 is highly expressed in GC and is associated with poor prognosis. Kaplan-Meier and ROC analyses demonstrated VAT1's potential in GC diagnosis, while multivariate analysis confirmed its role as an independent risk factor. Gene set enrichment analysis indicated that VAT1 plays a role in regulating the MAPK signaling pathway and epithelial-mesenchymal transition (EMT) in GC. Immune infiltration analysis showed a positive correlation between VAT1 and immune cells, particularly macrophages, and a negative correlation with chemotherapy sensitivity. In vitro and in vivo experiments further confirmed VAT1's critical role in promoting GC cell proliferation and inhibiting apoptosis. Overall, VAT1 holds significant value not only in GC diagnosis and prognosis but also as a potential target for immunotherapy and overcoming drug resistance.

Unveiling Molecular Dynamics of MeCp2, CDKL5 and BDNF in the Hippocampus of Individuals With Intractable Mesial Temporal Lobe Epilepsy.

Mutations occurring in the MeCp2, CDKL5 and BDNF genes have been linked to epileptogenesis in various epilepsy syndromes. This study employed bioinformatics analysis of transcriptomic data to examine the interrelationship among these genes in both epileptic and healthy individuals. Moreover, we assessed the expression of MeCp2, CDKL5 and BDNF at both mRNA and protein levels in human hippocampal tissues obtained from 22 patients undergoing epilepsy surgery for mesial temporal lobe epilepsy (MTLE) as well as from 25 autopsied specimens. Bioinformatics findings suggest that MeCp2, CDKL5 and BDNF genes play a role in regulating genes associated with epilepsy and disruptions in these genes may contribute to epilepsy development. Furthermore, the study reveals significantly lower MeCp2 and CDKL5 protein levels in the epileptic hippocampus compared to controls. Positive correlations are observed between MeCp2 and CDKL5 mRNA expression in autopsied samples and between CDKL5 and BDNF mRNA expression in epileptic hippocampal tissues. Differences in mRNA expression correlation patterns of MeCp2 and CDKL5 with BDNF are found between epileptic and control hippocampal tissues. Moreover, a significant positive correlation between MeCp2 and CDKL5 protein expression is noted in control hippocampal tissues. Our data suggest that altered expression of MeCp2, CDKL5 and BDNF within the hippocampus may contribute to epileptogenic processes in MTLE, impacting seizure characteristics, surgical outcomes and responses to antiepileptic drugs. Alterations in the expression of MeCp2, CDKL5 and BDNF within the hippocampus might contribute to the epileptogenic processes in MTLE. These changes could be linked to distinct functional consequences in epilepsy.

Comparing the cannabidiol-induced transcriptomic profiles in human and mouse Sertoli cells.

Cannabidiol (CBD), a major cannabinoid found in Cannabis sativa L., has been used in the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. Recently, concerns have been raised regarding the male reproductive toxicity of CBD in animal models, such as monkeys, rats, and mice. In our previous studies, we reported that CBD inhibited cell proliferation in both primary human Sertoli cells and mouse Sertoli TM4 cells. Transcriptomic analysis revealed that in primary human Sertoli cells CBD disrupted DNA replication, cell cycle, and DNA repair, ultimately causing cellular senescence. In this study, we further investigated the molecular changes induced by CBD in mouse Sertoli TM4 cells using RNA-sequencing analyses and compared the transcriptomic profile with that of primary human Sertoli cells. Our findings demonstrated that, unlike in primary human Sertoli cells, CBD did not induce cellular senescence but caused apoptosis in mouse Sertoli TM4 cells. Through transcriptomic data analysis in mouse Sertoli TM4 cells, immune and cellular stress responses were identified. Moreover, transcriptomic comparisons revealed major differences in molecular changes induced by CBD between mouse Sertoli TM4 and primary human Sertoli cells. This suggests that primary human Sertoli cells and mouse Sertoli cells may respond differently to CBD.

Screening of key genes involved in endometritis in cows and the regulatory role of CD83 in bovine endometrial epithelial cells.

Endometritis in dairy cows involves complex molecular regulatory mechanisms. Therefore, uncovering the molecular regulatory mechanisms of endometritis in dairy cows is crucial to understand its development, prevention, and treatment. This study aimed to screen and validate key genes associated with endometritis using transcriptome sequencing of blood samples and previously obtained metabolomic sequencing data. Based on gain-of-function and loss-of-function experiments on the gene, multiple techniques, including qRT-PCR, western blotting, detection of reactive oxygen species (ROS), measurement of mitochondrial membrane potential, EdU assay, flow cytometry, and CCK-8 assay were used to explore the function of the key gene in lipopolysaccharide (LPS)-stimulated bovine endometrial epithelial cells (BEECs). The results identified 536 differentially expressed genes (DEGs) between healthy cows and those with endometritis. These DEGs were significantly enriched in apoptosis and HIF-1 signaling pathways. Weighted gene co-expression network analysis of transcriptomic and metabolomic data identified CD83, CTNNAL1, LRRC25, and NR1H3 as potential key genes for endometritis in dairy cows, with CD83 being more significantly expressed in LPS-induced BEECs. Consequently, in vitro functional studies were performed on CD83. In overexpression experiments, downregulation of the expression of inflammatory markers interleukin (IL)-1β, IL-6, and IL-8 and reduced ROS release primarily indicated the role of CD83 in attenuating the inflammatory response of BEECs. Furthermore, overexpression of CD83 regulated the S/G2 phase transition of BEECs by affecting the mRNA and protein expression of proliferation marker genes, thereby promoting proliferation of BEECs. The increased EdU positivity and the cell proliferation rate further provided evidence for the promotion of cell proliferation after overexpression of CD83. Additionally, overexpression of CD83 attenuated LPS-stimulated mitochondrial damage in BEECs, as well as the downregulation of apoptosis marker gene expression. In contrast, knockdown of CD83 expression showed the opposite trend. In summary, CD83 attenuated the inflammatory response of BEECs, promoted their proliferation, and inhibited apoptosis. This study provided basic data for understanding the mechanisms of endometritis regulation at the gene level in dairy cows.

Model-driven engineering of Cutaneotrichosporon oleaginosus ATCC 20509 for improved microbial oil production.

Increasing demand for palm oil has drastic effects on the ecosystem as its production is unsustainable. C. oleaginosus is a yeast with great potential for microbial oil production and is a sustainable alternative to palm oil. Herein we deployed the Design-Build-Test-Learn approach to establish C. oleaginosus as an efficient fatty acid production platform. In the design step, we combined transcriptome data analysis and metabolic modeling and selected gene overexpression targets (ATP-citrate lyase, acetyl-CoA carboxylase, threonine synthase, and hydroxymethylglutaryl-CoA synthase) and media supplements (biotin, thiamine, threonine, serine, and aspartate). Characterization of transformants at various C/N ratios, and medium supplements provided up to 56% (w/w) lipid content and a 1.4-fold increase in lipid yield on glycerol (g/g). Additionally quadratic regressions suggested C/N ratio of 240 as the optimum value. These results and introduced pipeline for strain and medium optimization establish C. oleaginous as a sustainable alternative to palm as an oil source.

Metabolomic and Transcriptomic Analyses Reveal the Factors Underlying Mature Fruit Pericarp Color Variations in the ‘Xinli No. 7’ Pear (Pyrus sinkiangensis)

Background/Objectives: The ‘Xinli No. 7’ pear is a new pear variety with the advantages of early ripening, high quality, high storage resistance, and a long shelf life. Peel color is an important appearance-related trait and an important indicator of fruit quality and commercial value. Methods: In this study, we investigated the polyphenol compound biosynthesis metabolic pathway in the fruit pericarp of ‘Xinli No. 7’ pear using metabolomic and transcriptomic approaches, and qRT–PCR was used for the relative expression analysis of 21 DEGs associated with flavonoid biosynthesis. Results: A total of 128 phenolic compounds were identified, along with 1850 differently expressed genes (DEGs) in peels of different colors. Caftaric acid, apigenin, astragalin, phlorizin, prunin, taxifolin, rutin, naringenin, and their derivatives were abundant in the peel of ‘Xinli No. 7’ pear. An integrated analysis of transcriptomic and metabolomic data revealed that one1 PGT1, one LAR, two ANS, three 4CL, one CHS, one DFR, and one CHI gene involved in flavonoid biosynthesis exhibited markedly different expression levels in the fruit pericarp of ‘Xinli No. 7’ pear. Metabolic profiling of pear skin led to the identification of polyphenol substances involved in the flavonoid biosynthetic process and revealed 16 flavonoid compounds with high accumulation in pear fruit with red skin (PR). Notably, MYBs (25), bHLHs (18), WRKYs (15), NACs (15), ERFs (15), and MADs (2) may also contribute to the accumulation of flavonoid metabolites and the biosynthesis of anthocyanins in the peel of ‘Xinli No. 7’. Conclusions: Therefore, our results demonstrate the key role of phenolic compounds and candidate transcription factors involved in the peel color formation of ‘Xinli No. 7’ pear fruit.

Pharmacological effects of osimertinib on a chicken chorioallantoic membrane xenograft model with the EGFR exon-19-deleted advanced NSCLC mutation.

Non-small cell lung cancer (NSCLC) affects 10-50% of patients with epidermal growth factor receptor (EGFR) mutations. Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) that radically changes the outcome of patients with tumors bearing EGFR sensitizing or EGFR T790M resistance mutations. However, resistance usually occurs, and new therapeutic combinations need to be explored. The chorioallantoic membrane (CAM) xenograft model is ideal for studying aggressive tumor growth and the responses to complex therapeutic combinations due to its vascularization and complex microenvironment. This study aims to demonstrate the relevance of analyzing a complex therapeutic response to osimertinib treatment, especially through advanced transcriptomic analysis with the CAM model, which has been limited thus far. We engrafted HCC827 cells (EGFR p.E746_A750del) into the CAM model and treated them with various osimertinib doses for 7 days. The study involved supervised multivariate discrimination and ontology analysis of human transcriptional data. We found that CDX tumor growth inversely correlated with osimertinib dosage, with a notable 35% tumor weight reduction at 10 μm. Transcriptomic analysis revealed that osimertinib reduces EGFR pathway activity and its effectors, and dampens chemotaxis, immune recruitment and angiogenesis, indicating that effectiveness extends beyond cellular mechanisms to the tissue level. This was supported by a 15% reduction in blood vessels around the xenograft in osimertinib-treated cases. This study is the first to demonstrate that ontological analysis of transcriptomic data in the CAM model aligns with clinical observations, highlighting the relevance of this methodology for understanding and ameliorating the efficacy of targeted therapy in NSCLC.

Genome-wide identification and expression analysis of GRAS transcription factors under cold stress in diploid and triploid Eucalyptus

The GRAS [GRI (Gibberellic Acid Insensitive), RGA (Repressor of GAI-3 mutant), and SCR (Scarecrow)] transcription factors play a pivotal role in the development and stress responses of plants. Eucalyptus is an important fast-growing tree species worldwide, yet its poor cold tolerance limits its cultivation range. This study conducted a bioinformatics analysis of Eucalyptus grandis GRAS family and investigated the expression patterns of GRAS genes in different ploidy Eucalyptus under cold treatment. This study identified 92 EgrGRAS genes, which were divided into eight subfamilies. Interspecies synteny analysis found that E. grandis and Populus trichocarpa have more syntenic GRAS gene pairs. Chromosome localization analysis revealed that 90 EgrGRAS genes were found to be unevenly distributed across 11 chromosomes. Gene structure analysis found similar intron-exon structures in EgrGRAS genes. Protein motif analysis revealed that proteins within the same subfamily have certain structural similarities. The physical and chemical properties of the proteins encoded by EgrGRAS genes vary, but the ranges of amino acid numbers, molecular weights, and isoelectric points (pI) are similar to those of GRAS proteins from other species. Subcellular localization prediction using software found that 56 members of EgrGRAS family are localized in the nucleus, with a few members localized in the cytoplasm, chloroplasts, and mitochondria. Tobacco subcellular localization experiments verified a nuclear-localized GRAS transcription factor. Cis-acting element analysis predicted that EgrGRAS genes are involved in the growth as well as the response to hormones, light induction, and low-temperature stress. Transcriptome data analysis and quantitative real-time PCR (qRT-PCR) experiments in diploid and triploid Eucalyptus urophylla found that some EgrGRAS genes exhibited upregulated expression under different cold treatment durations, with certain genes from the LISCL, PAT1, and DELLA subfamilies significantly upregulated in triploid Eucalyptus. These EgrGRAS transcription factors may play an important role in Eucalyptus response to cold stress. The study lays a molecular foundation for the breeding of cold-resistant Eucalyptus varieties.

VIBE: an R-package for VIsualization of Bulk RNA Expression data for therapeutic targeting and disease stratification

BackgroundDevelopment of cancer treatments such as antibody-based therapy relies on several factors across the drug-target axis, including the specificity of target expression and characterization of downstream signaling pathways. While existing tools for analyzing and visualizing transcriptomic data offer evaluation of individual gene-level expression, they lack a comprehensive assessment of pathway-guided analysis, relevant for single- and dual-targeting therapeutics. Here, we introduce VIBE (VIsualization of Bulk RNA Expression data), an R package which provides a thorough exploration of both individual and combined gene expression, supplemented by pathway-guided analyses. VIBE’s versatility proves pivotal for disease stratification and therapeutic targeting in cancer and other diseases.ResultsVIBE offers a wide array of functions that streamline the visualization and analysis of transcriptomic data for single- and dual-targeting therapies. Its intuitive interface allows users to evaluate the expression of target genes and their associated pathways across various cancer indications, aiding in target and disease prioritization. Metadata, such as treatment or number of prior lines of therapy, can be easily incorporated to refine the identification of patient cohorts hypothesized to derive benefit from a given drug. We demonstrate how VIBE can be used to assist in indication selection and target identification in three user case studies using both simulated and real-world data. VIBE integrates statistics in all graphics, enabling data-informed decision-making.ConclusionsVIBE facilitates detailed visualization of individual and cohort-level summaries such as concordant or discordant expression of two genes or pathways. Such analyses can help to prioritize disease indications that are amenable to treatment strategies such as bispecific or monoclonal antibody therapies. With this tool, researchers can enhance indication selection and potentially accelerate the development of novel targeted therapies with the goal of precision, personalization, and ensuring treatments align with an individual patient’s disease state across a spectrum of disorders. Explore VIBE’s full capabilities using the vignettes on the GitLab repository (https://gitlab.com/genmab-public/vibe).

Targeting the Neuro-vascular Presynaptic Signalling in STROKE: Evidence and Therapeutic Implications.

Stroke is one of the leading causes of death and long-term adult disability worldwide. Stroke causes neurodegeneration and impairs synaptic function. Understanding the role of synaptic proteins and associated signalling pathways in stroke pathology could offer insights into therapeutic approaches as well as improving rehabilitation-related treatment regimes. The current study aims to analyse synaptic transcriptome changes in acute and long-term post-stroke (1 day, 7 day timepoints), especially focusing on pre- and postsynaptic genes. We performed data mining of the recent mRNA sequence from isolated mouse brain micro-vessels (MBMVs) after transient middle cerebral artery occlusion (tMCAO) stroke model. Using the SynGO (Synaptic Gene Ontologies and annotations) bioinformatics platform we assessed synaptic protein expression and associated pathways, and compared synaptic protein changes at 1 day and 7 day post-stroke. Enrichment analysis of the MBMVs identified significant alterations in the expression of genes related to synaptic physiology, synaptic transmission, neuronal structure, and organisation. We identified that the synaptic changes observed at the 7 day timepoint were initiated by the regulation of specific presynaptic candidates 1 day (24h) post-stroke, highlighting the significance of presynaptic regulation in mediating organising of synaptic structures and physiology. Analysis of transcriptomic data from human postmortem stroke brains confirmed similar presynaptic signalling patterns. Our findings identify the changes in presynaptic gene regulation in micro-vessels following ischaemic stroke. Targeting presynaptic active zone protein signalling could represent a promising therapeutic target in mitigating ischaemic stroke.

Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer

Objective: To investigate the preclinical efficacy and identify predictive biomarkers of polo-like kinase 1 (PLK1) inhibitors in small cell lung cancer (SCLC) models. Methods: We tested the cytotoxicity of selective PLK1 inhibitors (rigosertib, volasertib, and onvansertib) in a panel of SCLC cell lines. We confirmed the therapeutic efficacy of subcutaneous xenografts of representative cell lines and in four patient-derived xenograft models generated from patients with platinum-sensitive and platinum-resistant SCLC. We employed an integrated analysis of genomic and transcriptomic sequencing data to identify potential biomarkers of the activity and mechanisms of resistance in laboratory-derived resistance models. Results: Volasertib, rigosertib, and onvansertib showed strong in vitro cytotoxicity at nanomolar concentrations in human SCLC cell lines. Rigosertib, volasertib, and onvansertib showed equivalent efficacy to that of standard care agents (irinotecan and cisplatin) in vivo with significant growth inhibition superior to cisplatin in PDX models of platinum-sensitive and platinum-resistant SCLC. There was an association between YAP1 expression and disruptive or inactivation TP53 gene mutations, with greater efficacy of PLK1 inhibitors. Comparison of lab-derived onvansertib-resistant H526 cells to parental cells revealed differential gene expression with upregulation of NAP1L3, CYP7B1, AKAP7, and FOXG1 and downregulation of RPS4Y1, KDM5D, USP9Y, and EIF1AY highlighting the potential mechanisms of resistance in the clinical setting. Conclusions: We established the efficacy of PLK1 inhibitors in vitro and in vivo using PDX models of platinum-sensitive and resistant relapsed SCLC. An ongoing phase II trial is currently testing the efficacy of onvansertib in patients with SCLC (NCT05450965).

DSCT: A novel deep learning framework for rapid and accurate spatial transcriptomic cell typing

Abstract Unraveling the complex cell-type composition and gene expression patterns at the cellular spatial resolution is crucial for understanding intricate cell functions in the brain. In this study, we developed Deep Neural Network-based Spatial Cell Typing (DSCT), an innovative framework for spatial cell typing within spatial transcriptomic datasets. This approach utilizes a synergistic integration of an enhanced gene selection strategy and a lightweight deep neural network for data training, offering a more rapid and accurate solution for the analysis of spatial transcriptomic data. Based on comprehensive analysis, DSCT achieved exceptional accuracy in cell-type identification across various brain regions, species, and spatial transcriptomic platforms. It also performed well in mapping finer cell types, thereby showcasing its versatility and adaptability across diverse datasets. Strikingly, DSCT exhibited high efficiency and remarkable processing speed, with fewer computational resource demands. As such, this novel approach opens new avenues for exploring the spatial organization of cell types and gene expression patterns, advancing our understanding of biological functions and pathologies within the nervous system.

Screening of Oxidative Stress-related Biomarkers and Antioxidant Drugs for Polycystic Ovary Syndrome Based on Bioinformatics and Molecular Docking.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting women of reproductive age. Oxidative stress (OS) is suggested to play a significant role in the development of PCOS. Using antioxidants to reduce OS and maintain a healthy balance in the body could be a novel treatment approach for PCOS. This study analyzed transcriptome data from the Gene Expression Omnibus database, focusing on genes associated with OS. By implementing two machine learning algorithms, three OS-related biomarkers-HMOX1, MMP9, and KLF2-were successfully identified. To evaluate the diagnostic potential of these biomarkers, a Logistic regression model was employed. Additionally, granulosa cells were collected from healthy individuals and infertile women with PCOS, and the reliability of HMOX1, MMP9, and KLF2 was verified by quantitative real-time PCR experiments. Furthermore, small molecule drugs targeting proteins encoded by genes HMOX1 and MMP9 were predicted through the Drug Signature Database. Molecular docking of drugs to proteins identified two antioxidants, butein and demethoxycurcumin, as potential candidates for PCOS therapy.

Integrated Metabolomic and Transcriptomic Analysis Revealed the Mechanism of BHPF Exposure in Endometrium

Fluorene-9-bisphenol (BHPF) has been increasingly used as a bisphenol A substitute in the synthesis of various products. Previous studies have suggested that BHPF can be released from plastic bottles into drinking water, and BHPF accumulation has been reported to cause various adverse effects in humans. Nevertheless, the impact of BHPF exposure on endometrial epithelial cells remains largely unexplored. Here, we investigated the effects of exposure to different concentrations of BHPF on endometrial cells and used integrated metabolomic and transcriptomic methods to elucidate the underlying molecular mechanisms. Our results revealed significant associations between specific metabolites and genes, indicating that low-concentration exposure to BHPF affects endometrial epithelial cells by targeting pathways related to primary immunodeficiency, in which the key genes are IL7R and PTPRC. High-concentration exposure to BHPF decreased cell viability by regulating the purine metabolism pathway, as well as dysregulating the expression of PGM1, PDE3B, AK9, and ENTPD8. Our study highlights that the health risk of BHPF exposure to endometrial epithelial cells is concentration-dependent and that integrated analysis of metabolomic and transcriptomic data not only revealed the biological effects of BHPF and its underlying mechanisms, but also provided key candidate target genes for further exploration.

Loss of flavonoids homeostasis leads to pistillody in sua-CMS of Nicotiana tabacum

The homeotic transformation of stamens into pistil-like structures (pistillody) causes cytoplasmic male sterility (CMS). This phenomenon is widely present in plants, and might be induced by intracellular communication (mitochondrial retrograde signaling), but its systemic regulating mechanism is still unclear. In this study, morphological observation showed that the stamens transformed into pistil-like structures, leading to flat and dehiscent pistils, and fruit set decrease in sua-CMS (MS K326, somatic fusion between Nicotiana. tabacum L. K326 and Nicotiana suaveolens). Transcriptome data analysis presented that the expression levels of B-class MADS genes, including pMADS1, GLO1, GLO2, pMADS2.1, pMADS2.2, significantly reduced in the pistil-like structure of sua-CMS. DEGs were enriched in flavonoid and phenylpropanoid biosynthesis pathways. Transcriptome and metabolomics analysis revealed that the expression levels of CHI/CHS (key enzymes regulating flavonoid synthesis), and the contents of flavonoids reduced significantly in the pistil-like structures of sua-CMS. Chemical fluorescence staining assay showed that reactive oxygen species (ROS) levels were higher in the pistil-like structure of sua-CMS. Application of external flavonoids (hesperetin) reduced the frequency of pistillody and ROS levels. These results suggested that the metabolism of flavonoids played important roles in regulating pistillody through ROS in sua-CMS. Our study provides new insights into the regulatory mechanism of pistillody in plants.

Metabolomics Combined with Transcriptomics Reveals the Formation Mechanism of Different Colored Flowers of Cosmos bipinnata Cav

In nature, plants have rich and vivid colors. Flower color can confer economic and ornamental value to ornamental plants, and is one of the target traits for current directed breeding. Therefore, it is essential to understand the molecular regulatory mechanisms behind flower color formation in ornamental plants. However, in Cosmos bipinnata Cav., one of the most important ornamental plants, the metabolic pathways and molecular regulatory mechanisms underlying the formation of different flower colors are not yet clear, which greatly restricts the molecular breeding of flower color varieties. We selected three varieties of Cosmos bipinnata Cav. with white, pink, and red flowers as research materials, and identified significantly different metabolites among them through ultra performance liquid chromatography mass spectrometry (UPLC-MS/MS) analysis and principal component analysis (PCA). Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and transcriptome sequencing analysis in different colors flowers were used to reveal that the differential metabolites were enriched in flavonoid metabolic pathways and related structural genes were differentially expressed. Furthermore, we identified differentially expressed members of the MYB and bHLH transcription factor families, which play key roles in regulating the anthocyanin biosynthesis. By constructing a phylogenetic tree and performing a joint analysis of transcriptome and metabolome data, we further elucidated the molecular regulatory network underlying the formation of flower colors in Cosmos bipinnata Cav. This study not only provides a theoretical basis and gene resources for color-oriented breeding and the creation of new color varieties, but also offers new insights into the molecular mechanisms of flower color formation in plants.

Identification of the clinical and genetic characteristics of gliomas with gene fusions by integrated genomic and transcriptomic analysis

The identification of oncogenic gene fusions in diffuse gliomas may serve as potential therapeutic targets and prognostic indicators, representing a novel strategy for treating gliomas consistent with the principles of personalized medicine. This study identified detectable oncogene fusions in glioma patients through an integrated analysis of genomic and transcriptomic data, which encompassed whole exon sequencing and next-generation RNA sequencing. In addition, this study also conducted a comparison of the genetic characteristics, tumor microenvironment, mutation burden and survival between glioma patients with or without gene fusions. A total of 68 glioma patients were enrolled in this study, including glioblastoma (GBM), low grade glioma (LGG) and diffuse midline glioma (DMG). 14 cases of GBM patients (51.9%, 14/27) were found to harbor the following 70 oncogenic gene fusions: ROS1 (n = 8), NTRK (n = 5), KIF5 (n = 5), RET (n = 3) and other infrequent gene fusions (n = 49). A total of 11 gene fusions were identified in 8 LGG patients (32.0%, 8/25) and seven gene fusions were identified in one DMG patient (16.7%, 1/6). In GBM patient group, five genes including HOXA3, ACTB, CDK5, GNA12 and CARD11 exhibited a statistically significant higher copy number amplification frequency in the GBM group without gene fusions compared to that in the GBM group with gene fusions. In LGG patient group, CDK5 gene was also found to exhibit a statistically significant higher amplification frequency in the LGG group without gene fusions. In addition, KMT2D exhibited a statistically significant higher mutation frequency in the LGG group with gene fusions compared to that in the LGG group without gene fusions. Comparison of the other genetic characteristics including immune cell infiltration score, tumor mutation burden (TMB), and microsatellite instability (MSI). The results showed no statistically significant differences were observed between fusion and non-fusion group of GBM and LGG. The survival analysis revealed that GBM patients without gene fusions exhibited a longer median survival (737 days) compared to GBM patients with gene fusions (642 days), but without a statistical significancy. Our study has identified a set of gene fusions present in gliomas, including a number of novel gene fusions that have not been previously reported. We have also elucidated the underlying genetic characteristics of glioma with gene fusions. Collectively, our findings have the potential to inform future clinical treatment strategies for patients with glioma.

Integrated transcriptomic and metabolomic analyses elucidate the mechanism by which grafting impacts potassium utilization efficiency in tobacco

BackgroundPotassium plays a crucial role in determining the quality of flue-cured tobacco leaves. Our prior investigations have demonstrated that using potassium-efficient rootstocks through grafting offers a viable solution to the prevalent issue of low potassium levels in Chinese flue-cured tobacco leaves. Nevertheless, the specific molecular mechanisms responsible for the increase in potassium content following grafting in tobacco leaves have yet to be elucidated. This study revealing for the first time how grafting improves potassium utilization efficiency through combined transcriptome and metabolome analysis.ResultsThis study selected Wufeng NO. 2, a potassium-efficient variety, and Yunyan 87, a main cultivar, as the research subjects to investigate the underlying reasons for differential potassium utilization efficiency among different tobacco rootstocks through transcriptome and metabolic data analysis of grafted tobacco. The results showed a considerable increment of 90.1% in the potassium content of the grafted tobacco leaves. Overall, 2044 differentially expressed genes were identified through transcriptome analysis, with the majority being enriched in plant hormone signal transduction and the MAPK pathway. Metabolome analysis revealed 175 metabolites with significant differences, primarily involving primary metabolites such as amino acids and carbohydrates. Among these, there was an increase in the metabolites levels related to glycolysis, amino acid metabolism, and the TCA cycle pathway in grafted tobacco leaves. The key metabolites and genes in the above pathways were selected for Mantel-Pearson correlation analysis, leading to the identification of 2 genes and 3 metabolites, including IAA, CIP1, D-fructose, Fumaric acid and Oxoglutaric acid, that were significantly associated with the increased potassium content in grafted tobacco.ConclusionsThis study uncovers the intricate molecular mechanism behind grafting tobacco to enhance potassium utilization efficiency, thereby offering theoretical support for enhancing crop nutrient utilization efficiency through grafting technology.