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PubMed2006

New perspectives on host-parasite interplay by comparative transcriptomic and proteomic analyses of Schistosoma japonicum.

Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ~ 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay.

Amino Acid Sequence↗

PubMed2006

Transcriptome and proteome profiling to understanding the biology of high productivity CHO cells.

A combined transcriptome and proteome analysis was carried out to identify key genes and proteins differentially expressed in Chinese hamster ovary (CHO) cells producing high and low levels of dhfr-GFP fusion protein. Comparison of transcript levels was performed using a proprietary 15K CHO cDNA microarray chip, whereas proteomic analysis was performed using iTRAQ quantitative protein profiling technique. Microarray analysis revealed 77 differentially expressed genes, with 53 genes upregulated and 24 genes downregulated. Proteomic analysis gave 75 and 80 proteins for the midexponential and stationary phase, respectively. Although there was a general lack of correlation between mRNA levels and quantitated protein abundance, results from both datasets concurred on groups of proteins/genes based on functional categorization. A number of genes (20%) and proteins (45 and 23%) were involved in processes related to protein biosynthesis. We also identified three genes/proteins involved in chromatin modification. Enzymes responsible for opening up chromatin, Hmgn3 and Hmgb1, were upregulated whereas enzymes that condense chromatin, histone H1.2, were downregulated. Genes and proteins that promote cell growth (Igfbp4, Ptma, S100a6, and Lgals3) were downregulated, whereas those that deter cell growth (Ccng2, Gsg2, and S100a11) were upregulated. Other main groups of genes and proteins include carbohydrate metabolism, signal transduction, and transport. Our findings show that an integrated genomic and proteomics approach can be effectively utilized to monitor transcriptional and posttranscriptional events of mammalian cells in culture.

Animals↗

PubMedDate not supplied

Transcriptomics and proteomics: tools for optimising phytoremediation activities.

Negligent industrial development has greatly contributed to environmental pollution through the contamination of water and soil by xenobiotic organic chemicals Remedial strategies to deal with chemical pollution require reliable methods to identify and monitor contamination, as well as effective procedures to attenuate or to eliminate the pollutant. In the food chain, plants are ideally placed as early bio-indicators of environmental pollution as they experience and respond to environmental toxicants sooner than organisms at higher trophic levels. Furthermore, some plants are capable of detoxifying anthropogenic chemicals by metabolic transformation and could prove useful for the remediation of contaminated water and soil: so-called phytoremediation. So far research technologies aimed at developing plants for bio-indication/bio-monitoring and for remediation have largely relied on standardised chemical and biochemical procedures to evaluate phytotoxicity, metabolic fate and persistence of organic pollutants in plants. The next stage in the evolution of these plant-based technologies is the improvement and optimisation of any innate phytoremediation activities identified in selected plants. In general, uptake followed by metabolism and compartmentation is responsible for the detoxification of organic xenobiotics in plants. These are complex cellular systems that may be organised in well-defined pathways and are often controlled by large families of genes. In order to elucidate complex traits such as detoxification, an emerging idea is to make use of global approaches such as the new "omic" technologies to identify molecular changes in plant tissues exposed to specific organic xenobiotics. From expression profiles at the messenger RNA level, transcriptomics permit the identification of function-related gene clusters and at the protein level proteomics provide information on where, when and at what level specific proteins accumulate. We conclude that these global approaches may be a useful way of widening screening capability to identify appropriate molecular markers that can be used to improve detoxification activity.

Arabidopsis↗

PubMed2006

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

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

Adenosine Triphosphate↗

PubMed2005

Presenilin-1-dependent transcriptome changes.

Familial forms of Alzheimer's disease (FADs) are caused by the expression of mutant presenilin 1 (PS1) or presenilin 2. Using DNA microarrays, we explored the brain transcription profiles of mice with conditional knock-out of PS1 (cKO PS1) in the forebrain. In parallel, we performed a transcription profiling of the hippocampus and frontal cortex of the FAD-linked DeltaE9 mutant transgenic (TG) mice and matched controls [TG mice expressing wild-type human PS1 (hPS1)]. When the TG and cKO datasets were cross-compared, the majority of the 30 common expression alterations were in opposite direction, suggesting that the FAD-linked PS1 variant produces transcriptome changes primarily by gain of aberrant function. Our microarray studies also revealed an unanticipated inverse correlation of transcript levels between the brains of mice that coexpress DeltaE9 hPS1+ amyloid precursor protein (APP)695 Swe and DeltaE9 hPS1 single transgenic mice. The opposite directionality of these changes in transcript levels must be a function of APP and/or APP derivatives.

Alzheimer Disease↗

PubMed2006

Embryo-induced transcriptome changes in bovine endometrium reveal species-specific and common molecular markers of uterine receptivity.

The endometrium plays a central role among the reproductive tissues in the context of early embryo-maternal communication and pregnancy. This study investigated transcriptome profiles of endometrium samples from day 18 pregnant vs non-pregnant heifers to get insight into the molecular mechanisms involved in conditioning the endometrium for embryo attachment and implantation. Using a combination of subtracted cDNA libraries and cDNA array hybridisation, 109 mRNAs with at least twofold higher abundance in endometrium of pregnant animals and 70 mRNAs with higher levels in the control group were identified. Among the mRNAs with higher abundance in pregnant animals, at least 41 are already described as induced by interferons. In addition, transcript levels of many new candidate genes involved in the regulation of transcription, cell adhesion, modulation of the maternal immune system and endometrial remodelling were found to be increased. The different expression level was confirmed with real-time PCR for nine genes. Localisation of mRNA expression in the endometrium was shown by in situ hybridisation for AGRN, LGALS3BP, LGALS9, USP18, PARP12 and BST2. A comparison with similar studies in humans, mice, and revealed species-specific and common molecular markers of uterine receptivity.

Animals↗

PubMed2005

Systems toxicology: applications of toxicogenomics, transcriptomics, proteomics and metabolomics in toxicology.

Toxicogenomics can facilitate the identification and characterization of toxicity, as illustrated in this review. Toxicogenomics, the application of the functional genomics technologies (transcriptomics, proteomics and metabolomics) in toxicology enables the study of adverse effects of xenobiotic substances in relation to structure and activity of the genome. The advantages and limitations of the different technologies are evaluated, and the prospects for integration of the technologies into a systems biology or systems toxicology approach are discussed. Applications of toxicogenomics in various laboratories around the world show that the crucial steps and sequence of events at the molecular level can be studied to provide detailed insights into mechanisms of toxic action. Toxicogenomics allowed for more sensitive and earlier detection of adverse effects in (animal) toxicity studies. Furthermore, the effects of exposure to mixtures could be studied in more detail. This review argues that in the (near) future, human health risk assessment will truly benefit from toxicogenomics (systems toxicology).

Animals↗

PubMed2006

Whole transcriptome amplification for gene expression profiling and development of molecular archives.

Expression profiling of clinically obtainable tumor specimens has been hindered by the need for microgram quantities of RNA. In vitro transcription (IVT)-based amplifications are most commonly used to amplify small quantities of RNA for microarray analysis. However, significant drawbacks exist with IVT-based amplification, and the need for alternative amplification methods remains. Herein, we validate whole transcriptome amplification (WTA), an exponential amplification technique that produces cDNA libraries and amplified target in 3 to 4 hours from nanogram quantities of total RNA using a combination of cDNA microarrays and quantitative polymerase chain reaction (PCR). We demonstrate that WTA material can serve as a "molecular archive" because a WTA cDNA library can be faithfully amplified through multiple rounds of PCR amplification, allowing it to serve as a bankable and distributable resource. To demonstrate applicability, WTA was combined with laser capture microdissection to profile frozen prostate tissues. Unlike most IVT-based and exponential amplification techniques, WTA does not depend on the presence of a poly-A tail. Thus, we demonstrate that WTA is compatible with artificially degraded RNA and RNA isolated from formalin-fixed paraffin-embedded tissues. Taken together, WTA represents a versatile approach to profile and archive cDNA from minute tumor samples and is compatible with partially degraded RNA.

Biological Specimen Banks↗

PubMed2005

Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state.

Human embryonic stem cells (hESCs) are an important source of stem cells in regenerative medicine, and much remains unknown about their molecular characteristics. To develop a detailed genomic profile of ESC lines in two different species, we compared transcriptomes of one murine and two different hESC lines by massively parallel signature sequencing (MPSS). Over 2 million signature tags from each line and their differentiating embryoid bodies were sequenced. Major differences and conserved similarities between species identified by MPSS were validated by reverse transcription polymerase chain reaction (RT-PCR) and microarray. The two hESC lines were similar overall, with differences that are attributable to alleles and propagation. Human-mouse comparisons, however, identified only a small (core) set of conserved genes that included genes known to be important in ESC biology, as well as additional novel genes. Identified were major differences in leukemia inhibitory factor, transforming growth factor-beta, and Wnt and fibroblast growth factor signaling pathways, as well as the expression of genes encoding metabolic, cytoskeletal, and matrix proteins, many of which were verified by RT-PCR or by comparing them with published databases. The study reported here underscores the importance of cross-species comparisons and the versatility and sensitivity of MPSS as a powerful complement to current array technology.

Animals↗

PubMed2005

In vitro expansion of human mesenchymal stem cells: choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability.

Human bone marrow mesenchymal stem cells (hMSCs) represent an appealing source of adult stem cells for cell therapy and tissue engineering, as they are easily obtained and expanded while maintaining their multilineage differentiation potential. All current protocols for in vitro culture of hMSCs include fetal bovine serum (FBS) as nutritional supplement. FBS is an undesirable additive to cells that are expanded for therapeutic purposes in humans because the use of FBS carries the risk of transmitting viral and prion diseases and proteins that may initiate xenogeneic immune responses. In the present study, we have therefore investigated if autologous serum (AS) or allogeneic human serum (alloHS) could replace FBS for the expansion of hMSCs in vitro. We discovered that the choice of serum affected hMSCs at several different levels. First, hMSCs in AS proliferated markedly faster than hMSCs in FBS, whereas use of alloHS resulted in hMSC growth arrest and death. Second, hMSCs in FBS differentiated more rapidly toward mesenchymal lineages compared with hMSCs in AS. Interestingly, genome-wide microarray analysis identified several transcripts involved in cell cycle and differentiation that were differentially regulated between hMSCs in FBS and AS. Finally, several transcripts, including some involved in cell cycle inhibition, were upregulated in hMSCs in FBS at a late passage, whereas the hMSC transcriptome in AS was remarkably stable. Thus, hMSCs may be expanded rapidly and with stable gene expression in AS in the absence of growth factors, whereas FBS induces a more differentiated and less stable transcriptional profile.

Animals↗

PubMed2004

The transcriptome profile of human embryonic stem cells as defined by SAGE.

Human embryonic stem (ES) cell lines that have the ability to self-renew and differentiate into specific cell types have been established. The molecular mechanisms for self-renewal and differentiation, however, are poorly understood. We determined the transcriptome profiles for two proprietary human ES cell lines (HES3 and HES4, ES Cell International), and compared them with murine ES cells and other human tissues. Human and mouse ES cells appear to share a number of expressed gene products although there are numerous notable differences, including an inactive leukemia inhibitory factor pathway and the high preponderance of several important genes like POU5F1 and SOX2 in human ES cells. We have established a list of genes comprised of known ES-specific genes and new candidates that can serve as markers for human ES cells and may also contribute to the "stemness" phenotype. Of particular interest was the downregulation of DNMT3B and LIN28 mRNAs during ES cell differentiation. The overlapping similarities and differences in gene expression profiles of human and mouse ES cells provide a foundation for a detailed and concerted dissection of the molecular and cellular mechanisms governing their pluripotency, directed differentiation into specific cell types, and extended ability for self-renewal.

Animals↗

PubMed2025

Comparative genomics and transcriptomics of the Spiroplasma glossinidia strain sGff reveal insights into host interaction and trypanosome resistance in Glossina fuscipes fuscipes.

Tsetse (Glossina spp.) are vectors of African trypanosomes, the causative agents of Human and African Animal trypanosomiases, diseases that remain significant medical and socioeconomic challenges in sub-Saharan Africa. In addition to trypanosomes, tsetse harbor both obligate and facultative symbiotic bacteria that can influence vector competence and reproductive biology. One such facultative symbiont, Spiroplasma glossinidia, infects several tsetse species within the Palpalis subgroup. In Glossina fuscipes fuscipes (Gff), the Spiroplasma glossinidia strain sGff induces a trypanosome-refractory phenotype and negatively impacts reproductive fitness by reducing female fecundity. However, the mechanisms behind these Spiroplasma-derived phenotypes remain poorly understood. Here, we report successful in vitro cultivation of sGff and present complete genomes from three sources: in vitro cultured sGff and sGff isolated from both laboratory-maintained and wild-caught (Uganda) Gff flies. Comparative genomic analyses revealed a high degree of similarity in gene content and synteny among these sGff samples, confirming that they represent isolates of the same strain. Phylogenomic analyses placed sGff within the Spiroplasma poulsonii clade. The sGff genome is highly dynamic, containing numerous mobile genetic elements. Additionally, in silico annotations indicate that sGff relies on its host for both lipids and carbohydrates and produces several toxins, all of which could be implicated in the observed trypanosome refractory phenotype. Finally, comparative transcriptomic analysis of sGff from host hemolymph versus in vitro culture provided insights into potential factors relevant to host-symbiont interactions. Our findings provide a foundation for understanding the nutritional dialogue between sGff and its host and identify symbiotic products that may contribute to trypanosome resistance. Furthermore, the establishment of an in vitro culture system for sGff represents a significant resource for future functional studies with potential implications for vector control.

Glossina fuscipes fuscipes↗

PubMed2026

Genome-wide cis-expression Quantitative Trait Loci (eQTL) and transcriptomic signals reveal distinct molecular regulation across correlated feed efficiency traits.

INTRODUCTION: Feed efficiency (FE) is a complex trait which determines livestock production profitability, yet the molecular mechanisms behind it remain unclear. This study investigated the blood transcriptomic profile of lambs, alongside genotype data with the aim to uncover the genetic basis of FE traits such as absolute dry matter intake (DMIabsolute), DMI adjusted for body size (DMIadjusted), average daily live weight gain (ADG), and residual feed intake (RFI). MATERIALS AND METHODS: Bulk RNA-Seq and genotype data were analysed using three complementary approaches: differential gene expression (DGE) analysis, weighted gene co-expression network analysis (WGCNA), and cis-expression Quantitative Trait Loci (cis-eQTL) mapping. These methods were used independently to identify genes and regulatory networks associated with FE traits and to investigate evidence supporting multi-trait candidate gene selection. RESULTS: DGE analysis revealed 2, 24, 85 and 4 differentially expressed genes for DMIabsolute, DMIadjusted, ADG, and RFI (Padjusted < 0.05), functionally enriched in sensory perception, ATP-dependent chromatin remodeling, Notch signaling and immune response pathways. 9 gene modules significantly associated with the FE traits (P ≤ 0.05) with correlations ranging from r = -0.56 to 0.49, were identified using WGCNA. Single nucleotide polymorphism (SNP)-level cis-eQTL analysis identified 93 eSNPs associated with 74 genes (false discovery rate (FDR) < 0.05), while permutation-derived gene level analysis identified 280 eGenes (FDR < 0.2, empirical P < 0.03). Across the three analyses, applying thresholds of DGE (Padjusted < 0.05), WGCNA (correlation, P ≤ 0.05), and cis-eQTL gene-level significance (empirical P < 0.05), multiple overlapping genes were identified including DNMT3A, KANSL1, NCOR1 for DMIadjusted, ACOX2, FANCF, CIMIP2B, LOC101115106, ARMH2, LOC132657496 for ADG, and LOC114114576 for RFI representing regulators of variations in FE. DISCUSSION: The integration of DGE, WGCNA, and cis-eQTL analyses identified key genes and regulatory mechanisms associated with variation in FE traits. These results highlight that integrated multi-trait candidate gene identification approaches can reveal key genes that lower feed intake while maintaining animal growth, supporting breeding strategies aimed at improving efficiency and long-term economic sustainability in sheep.

average daily gain (ADG)↗

PubMed2026

From transcriptomic profiling to precision oncology: a bibliometric analysis of RNA sequencing in acute myeloid leukemia.

BACKGROUND: RNA sequencing (RNA-seq) has become an important tool for investigating the molecular heterogeneity of acute myeloid leukemia (AML); however, the global development and thematic evolution of this field remain inadequately characterized. OBJECTIVE: To map the global landscape of AML RNA-seq research and identify major knowledge domains, emerging themes, and temporal changes in research priorities. METHODS: Publications indexed in the Web of Science Core Collection and Scopus between January 1, 2007, and August 18, 2025, were retrieved. After database filtering, merging, and deduplication, 3,460 articles and reviews were included. CiteSpace, VOSviewer, the bibliometrix R package, and Microsoft Excel were used to analyze publication trends, collaboration networks, co-citation structures, keyword evolution, and citation bursts. RESULTS: Publication output increased steadily, accelerating after 2014. China contributed the largest number of publications (n = 547, 15.8%), whereas the United States had the highest total citation count. Major publication outlets spanned hematology, oncology, genomics, and molecular biology. Co-citation analysis identified prominent themes involving next-generation sequencing, gene mutations, KMT2A rearrangements, epigenetic dysregulation, leukemia-initiating cells, drug resistance, biomarkers, T-cell biology, and single-cell sequencing. Earlier literature emphasized sequencing technologies, gene expression profiling, and molecular alterations, whereas recent publications show increasing representation of cellular heterogeneity, single-cell transcriptomics, drug resistance, biomarker applications, immune-related research, and computational interpretation. CONCLUSION: While molecular characterization remains foundational, AML RNA-seq research has broadened to encompass increasingly prominent cellular, functional, computational, and translational dimensions. This study provides a structured overview of the field; nevertheless, bibliometric prominence should not be interpreted as direct evidence of clinical utility.

RNA sequencing↗

PubMed2026

Integrative cross-tissue transcriptome-wide association and metabolomic analysis reveals novel genetic risk loci for aortic aneurysm.

BACKGROUND: Aortic aneurysm (AA) is a life-threatening cardiovascular condition with a strong genetic component, however, its molecular mechanisms remain poorly understood. Although genome-wide association studies (GWAS) have identified numerous risk loci, most prior studies have investigated genetic and metabolic factors separately, leaving the causal pathways from genetic variants to disease largely unexplored. METHODS: We established an integrative framework combining cross-tissue transcriptome-wide association studies (TWAS) with metabolomic mediation analysis. First, we integrated GWAS data from FinnGen R12 with multi-tissue expression quantitative trait loci (eQTL) data from Genotype-Tissue Expression Project (GTEx) V8, then performed cross-tissue TWAS using the Unified Test for MOlecular SignaTures (UTMOST) and single-tissue validation with the Functional Summary-based Imputation (FUSION) to prioritize susceptibility genes. Second, we applied Mendelian randomization (MR), colocalization, and Fine-mapping Of CaUsal gene Sets (FOCUS) to assess causality and identify high-confidence genes. Third, we performed metabolite mediation analysis to uncover metabolic pathways linking genetic variants to disease risk. Finally, we validated key findings in mouse models of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) using Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (RT-qPCR) and Western blotting. RESULTS: We identified multiple novel susceptibility genes for AA and its subtypes. Key genes included ADH family members (ADH1A, ADH1B, ADH4, ADH6) and ZNF827, which showed cross-subtype associations with strong colocalization evidence in vascular tissues. Metabolite mediation analysis revealed significant pathways involving N-acetylphenylalanine and methionine sulfoxide. Functional enrichment revealed distinct biological mechanisms: AA and AAA were primarily associated with metabolic pathways, whereas TAA-related genes were enriched in developmental and contractile processes. PheWAS indicated no significant off-target associations. Critically, experimental validation in mouse models confirmed significant upregulation of ZNF827 in TAA and ADH6 in AAA at both mRNA and protein levels, corroborating the genetic predictions. CONCLUSION: This integrated cross-omics analysis identifies novel genetic loci and, crucially, uncovers specific nutrient-related metabolic pathways that mediate genetic risk. These findings provide a mechanistic basis for future nutritional and metabolic intervention studies in AA and its subtypes.

MAGMA↗

PubMed2026

A minimal three-arm oral regimen for healthspan: mechanistic alignment with transcriptomic signals from a large parental-lifespan GWAS.

A large genome-wide association study of parental lifespan was reported in 2019. A later transcriptome-wide association study (TWAS) based on those summary statistics identified a set of transcriptional programs associated with longer genetically predicted survival, including increased brain NAD + salvage, especially NMNAT2, reduced glucose-stimulated insulin secretion, a shift toward synaptic pruning with less broad plasticity, and a glial pattern characterized by relatively greater microglial and lower astrocytic signatures, with only weak pan-tissue senescence signals. Building on those directional findings, this short communication proposes a minimal three-arm oral regimen with unequal evidentiary weight: first, the Cheung Glutamatergic Regimen, consisting of low-dose dextromethorphan potentiated by a CYP2D6 inhibitor together with piracetam and L-glutamine, as an exploratory adjunct aimed at preserving residual functional connectivity; second, daily nicotinamide mononucleotide and N-acetylcysteine with pulsed senolytics for NAD + salvage and senescence modulation; and third, GLP-1 receptor agonism for metabolic reprogramming. The NAD+/senescence arm is the primary mechanistic anchor, GLP-1 receptor agonism provides secondary metabolic support, and the glutamatergic arm is exploratory. Each arm targets a separate node within the pruning-plasticity-metabolic triad. The regimen is fully oral, uses conservative dosing, and draws on prior therapeutic or human-exposure data, although the proposed combination has no established safety profile. Although direct combination data are lacking and the foundational TWAS remains a preprint, the components show plausible but uneven mechanistic alignment with the TWAS signals and may justify carefully designed, safety-focused pilot evaluation.

GLP-1↗

PubMed2026

Transcriptomic Profiling of Canine Testicular Leydig Cell Tumors Uncovers Key Upregulated Gene Pathways.

Total RNA was isolated from sections of healthy testes and Leydig cell tumors of mixed-breed dogs using TMA Master II device. The RNA-seq libraries were sequenced on the Illumina platform. Following differential expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were applied with quality control obtained using FastQC and Trimmomatic. This analysis revealed 1500 transcripts, including 928 upregulated and 168 downregulated genes. The results demonstrated that a significant proportion of these differentially expressed genes are directly involved in the control of sex steroid production (CYP11A1, STAR, and 3β-HSD3B1) or tube formation, angiogenesis, and extracellular matrix remodeling in interstitial cells (ESM1, FGG, and VEGFA). Moreover, we identified the upregulation of transcripts responsible for neurotransmitter or neuroendocrine signaling (SLC6A4, GRIN2C, GABRB3) and cholesterol metabolism and its regulation (GPX3, MSMO1, DHCR24). These genes were strongly associated with the phosphatidylinositol-3-kinase (PI3K)-Protein Kinase B (Akt) cascade and extracellular matrix interactions, features shared with various malignancies. Alterations in estrogen and relaxin signaling appear to be distinctive, understudied mechanisms specific to canine Leydig cell tumors. Concurrently, downregulated genes (e.g., DMRTC2, SEMA3C, ALOX12) were linked with cell differentiation, signaling and immunoregulatory pathway suppression involved in tumorigenesis. A complex transcriptomic profile of canine Leydig cell tumors was developed, revealing a conserved oncogenic core shared in some aspects with human malignancies alongside unique species-specific alterations. Findings seem to be useful for identifying novel diagnostic biomarkers and targeted therapies in veterinary oncology, establishing canine reproductive tissues as a valuable comparative biomedical model for research in human.

Leydig cell tumor↗

PubMed2026

Integrated Metabolomic and Transcriptomic Analysis Reveals Tissue-Specific Secondary Metabolic Differentiation and Indole Alkaloid Accumulation in Evodia rutaecarpa.

Evodia rutaecarpa is a valuable medicinal plant, yet its non-medicinal tissues remain largely underexplored. Here, we integrated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based widely targeted metabolomics and RNA sequencing (RNA-seq) transcriptomics to systematically profile the metabolic and transcriptional landscapes of roots, stems, leaves, and flowers of Evodia rutaecarpa (Juss.) Benth. Our aim was to characterize tissue-specific metabolic differentiation and its underlying transcriptional regulatory mechanisms. Metabolomic analysis, employing principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) with robust model parameters (R2Y > 0.9, Q2 > 0.5), identified 3090 differential metabolite features (variable importance in projection, VIP > 1.0; p < 0.05) across the four tissues, which exhibited distinct tissue-specific clustering patterns. Integrated Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and weighted gene co-expression network analysis (WGCNA) revealed that roots specifically accumulated quinolone alkaloids and flavonoid glycosides, accompanied by the coordinated upregulation of genes involved in flavonoid and phenylpropanoid biosynthetic pathways. In contrast, stems, leaves, and flowers were enriched in indole alkaloids (evodiamine and rutaecarpine) and volatile oil precursors, with concurrent upregulation of genes involved in tryptophan metabolism and indole alkaloid biosynthesis (e.g., tryptophan decarboxylase, TDC; s N-methyltransferase, NMT). Notably, leaves and flowers displayed particularly high accumulation levels of these bioactive alkaloids, suggesting their potential as alternative sources for industrial and pharmaceutical applications. WGCNA further identified multiple transcription factors and structural gene modules tightly correlated with evodiamine accumulation, offering promising candidate regulators for future biosynthetic pathway engineering. Collectively, this multi-omics integration study systematically elucidates the tissue-partitioned secondary metabolism of Evodia rutaecarpa (Juss.) Benth. and provides a solid scientific foundation for full-plant resource utilization, targeted development of non-medicinal tissues, and future metabolic engineering of indole alkaloid production.

Evodia rutaecarpa↗