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Results for “cross-species transcriptomics”

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PubMed2026

Selective saccular plasticity under microgravity links peripheral transcriptomic remodeling to postflight vestibular dysfunction.

Long-duration exposure to microgravity disrupts human balance and spatial orientation, yet the molecular mechanisms underlying vestibular adaptation to spaceflight remain poorly understood. Here, we tested the hypothesis that the saccule, the primary gravity-sensing otolith organ, undergoes selective remodeling during spaceflight and contributes to transient postflight postural instability. Using a cross-species approach, we combined transcriptomic analysis of mouse otolith organs with physiological assessments in astronauts. Laser microdissection-based RNA sequencing of mouse otolith sensory epithelia after a 35-d spaceflight revealed pronounced, organ-specific transcriptomic remodeling in the saccule, whereas the utricle remained stable. Principal component and clustering analyses demonstrated that the saccular transcriptome shifted toward an utricle-like profile under microgravity, accompanied by changes in genes related to synaptic and neuronal function. Promoter motif analysis identified NFAT-associated transcriptional networks, suggesting Ca2+-dependent regulation of synaptic plasticity as a potential molecular substrate of gravity-dependent adaptation. In parallel, vestibular testing in astronauts following long-duration missions (157 to 328 d) revealed selective attenuation of saccule-mediated cervical vestibular-evoked myogenic potentials and increased postural sway immediately after return to Earth, while utricle-mediated responses and semicircular canal function were preserved. Both saccular function and postural stability recovered within approximately 10 d. Notably, early postflight postural instability was partially mitigated by noisy galvanic vestibular stimulation, consistent with stochastic resonance-mediated sensory enhancement. Together, these findings identify the saccule as a plastic gravity sensor and establish a mechanistic link between peripheral molecular remodeling and functional balance deficits after spaceflight, providing a framework for developing countermeasures to facilitate vestibular readaptation during human space exploration.

Animals↗

PubMed2026

Environmental benzene exposure induces a conserved neutrophil degranulation program across species.

Immune systems have evolved under constant pressure from pathogens and environmental challenges, leading to the emergence of conserved defense mechanisms across diverse organisms. Evidence indicates that environmental exposures perturb immune regulatory networks, particularly during development, when transcriptional programs governing hematopoiesis, immune cell differentiation, and inflammatory signaling are highly dynamic and sensitive to external stressors. Volatile organic compounds represent an important but incompletely understood source of immunological perturbation. Among these, benzene is a ubiquitous environmental contaminant associated with hematotoxicity and immune dysregulation; however, transcriptional responses to environmentally relevant low-level exposures during development remain poorly characterized. To determine whether benzene exposure engages conserved cross-species immune regulatory pathways, we performed a comparative transcriptomic analysis integrating developmental tissues from 3 vertebrate systems: human placenta, murine placenta, and zebrafish larvae. Bulk RNA sequencing datasets were analyzed to identify transcriptional responses associated with benzene exposure in experimental models (≤5 ppm) and with benzene adduct levels in maternal plasma for human samples. Because placental gene expression exhibits strong sexual dimorphism, murine datasets were stratified by fetal sex. Pathway- and network-level analyses were used to identify conserved biological responses. We observed a striking convergence on activation of innate immune pathways associated with neutrophil degranulation, IL-8 signaling, and Rho GTPase-mediated inflammatory responses. Further, network analyses identified CXCL8 and ERK1/2 as shared regulatory hubs linking transcriptional responses across datasets. Together, these findings uncover an evolutionarily conserved innate immune signature associated with benzene exposure during vertebrate development, suggesting that environmental chemical perturbations may disrupt fundamental immune regulatory programs across species.

Animals↗

PubMed2025

Through the lens of bioenergy crops: advances, bottlenecks, and promises of plant engineering.

Advances in engineering of bioenergy crops were driven over the past years by adapting technological breakthroughs and accelerating conventional applications but also exposed intriguing challenges. New tools revealed rich interconnectivity in the exponentially growing and dynamic 'big' omics data' of metabolomes, transcriptomes, and genomes at previously inaccessible magnitude (global, cross-species, meta-) and resolution (single cell). Insights enabled fresh hypotheses and stimulated disciplines such as functional genomics with discovery of broad regulatory networks and their determinants, that is, DNA parts, including promoters, regulatory elements, and transcription factors. Their rational design, assembly into increasingly complex blueprints, and installation into diverse chassis is an existing frontier that may benefit from emerging technologies to address bottlenecks. Interweaving nature-inspired to fully synthetic parts has already allowed building of fine-tuned regulatory circuits, or new-to-nature metabolic routes insulated from the biological context of the chassis species. Similarly, developments and the evolving need for unifying principles in plant transformation and species-agnostic technologies highlight future opportunities for engineering the next generation of bioenergy plants.

Crops, Agricultural↗

PubMed2026

scBaseCount: An AI agent-curated, standardized, auto-updated single-cell data repository.

Single-cell RNA sequencing has transformed cell biology by enabling precise transcriptomic measurements of individual cells. The Sequence Read Archive (SRA) is the largest public repository of sequencing reads, yet much of it remains underutilized due to unstandardized metadata. Here, we introduce scBaseCount, a database that leverages an AI agent to automate discovery and metadata extraction and standardize data processing. Built by mining all 10x Genomics datasets, scBaseCount is the largest public repository of single-cell gene expression data, comprising over 502 million cells across 27 organisms and 75 tissues. It offers an unbiased view of the data landscape within the SRA and enables the training of more performant computational models through access to broader phenotypic diversity. Uniform processing enables measurement of both intronic and exonic reads and non-coding gene expression and improves alignment across experiments. Moreover, scBaseCount provides a blueprint for how AI can be leveraged to autonomously curate biological data repositories.

Single-Cell Analysis↗

PubMed2025

Decoding nitrogen uptake efficiency in maize and sorghum: insights from comparative gene regulatory networks.

Nitrogen (N) is an essential macronutrient for plant growth and yield, yet optimizing nitrogen use efficiency remains a challenge in agriculture. To better understand the regulatory basis of plant responses to N availability, we constructed a maize-specific nitrogen uptake efficiency gene regulatory network (mNUEGRN) comprising 1625 protein-DNA interactions (PDI) between 70 promoters and 301 transcription factors using enhanced yeast one-hybrid assays. We also projected a sorghum NUE GRN (spNUEGRN) based on maize orthologs and analyzed N-responsive subnetworks in both species using transcriptome profiling under N stress of early deprivation and recovery. Cross-species comparison with an existing Arabidopsis GRN revealed about 18% conserved interaction, corresponding to 11% of the mNUEGRN, particularly within the nitrate assimilation pathways. Notably, bZIP18 and bZIP30 emerged as central regulators in mNUEGRN, forming highly connected feed-forward loops (FFLs). From our time series data, we identified 19 236 and 23 864 differentially expressed genes in maize and sorghum, respectively. Gini correlation analysis uncovered 764 and 638 FFLs in mNUEGRN and spNUEGRN, respectively, of which 22 FFLs in maize and 35 in sorghum were identified in both leaf and root for each species. These FFLs may represent candidate regulatory motifs that contribute to modulating transcriptional responses under fluctuating N conditions, but their potential roles require further investigation. Together, our findings reveal evolutionarily conserved and species-specific regulatory strategies that mediate early N responsiveness, offering a foundation for engineering crops with improved NUE.

Sorghum↗

PubMed2026

Longitudinal multiorgan transcriptomic atlas of salt-induced hypertension.

High dietary salt intake elevates blood pressure and drives multiorgan damage. However, the molecular programs underlying progressive organ injury remain poorly defined. Here, we present a longitudinal multiorgan transcriptomic atlas of salt-induced hypertensive injury. We profiled kidney cortex, kidney medulla, heart, and liver across 4 stages, spanning early hypertension to advanced pathology in Dahl salt-sensitive rats. We identified dynamic and tissue-specific molecular trajectories, including a shared early proliferative response that converges on proinflammatory and fibrotic remodeling. Notably, we uncovered compartment-specific renal responses, showing that the cortex and medulla, despite their proximity, follow distinct molecular trajectories during disease progression. We further identified 79 stage- and tissue-specific transcription factors that drive gene expression dynamics in salt-induced hypertensive injury. Integration with human genome-wide association studies revealed conserved pathways in endocrine signaling, ion transport, lipid metabolism, and detoxification, establishing cross-species relevance and highlighting mechanistic targets of clinical importance. Compound-transcriptome analysis revealed stage- and organ-specific therapeutic opportunities, prioritizing kinase and epigenetic modulators as candidates to rebalance maladaptive gene programs. Overall, this study provides a resource for understanding molecular mechanisms from early salt-induced hypertension to tissue-specific injury and underscores the need for precision interventions.

Animals↗

PubMed2026

RNA Virus Diversity, Cross-Species Transmission, and Molecular Constraints in Two Closely Related Rat Species.

Viral infection involves co-evolution with hosts, yet the molecular determinants that constrain viral cross-species transmission remain poorly understood. Here, we established conspecific and heterospecific co-housing models for two closely related rat species, Rattus norvegicus (RN) and Rattus tanezumi (RT), both maintained in laboratory settings for over 10 generations, together with wild-caught RT individuals. Using meta-transcriptomic sequencing and population genomic analyses, we compared their RNA virus profiles and investigated the potential molecular constraints on cross-species viral transmission. From 63 rats, we characterized an extensive RNA virome comprising more than 600 viruses, including 7 zoonotic viruses, 29 viruses with cross-species transmission potential, and 335 novel viruses. Notably, the prevalence of Seoul orthohantavirus (SEOV) was significantly higher in RN than in RT. Population genomic analysis revealed that RN exhibited higher heterozygosity in Itgb3 (the gene encoding the SEOV receptor, β3-integrin) and Tlr7 (the gene encoding the receptor for viral ssRNA, Toll-like receptor 7) compared to RT. These genetic variations likely represent the molecular determinants responsible for the differential susceptibility to SEOV between the two species. Our findings clarify the diversity and prevalence of RNA viruses in closely related rodent species and highlight host genetic barriers that may influence zoonotic spillover risk.

Animals↗

PubMed2021

Comparative cellular analysis of motor cortex in human, marmoset and mouse.

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

Animals↗

PubMed2026

Atherosclerotic plaque fibroblasts derive from adventitial and medial Pdgfra-lineage-positive cells and predominantly maintain fibroblast identity.

AIMS: Fibroblasts are mesenchymal cells in the healthy vascular adventitia. In atherosclerosis, single-cell sequencing datasets suggest fibroblasts are abundant in plaques. However, their identity, origin, and fate during plaque progression remain unclear, which we aim to unravel here. APPROACH AND RESULTS: To robustly define fibroblast identity, origin, and fate, we employed meta-analyses of 54 single-cell RNA sequencing libraries, including murine smooth muscle cell (Myh11) and endothelial cell (EC) (Cdh5) lineage reporter mice with and without atherosclerosis; human control and atherosclerotic arteries; and murine adventitia and atherosclerotic plaques processed separately from low-density lipoprotein (LDL) receptor knockout (Ldlr-/-) mice. These meta-analyses showed that murine and human plaque fibroblast identity was robustly defined by Pdgfra, Pi16, Cygb, and Serpinf1 mRNA. Ninety-five percent of plaque fibroblasts do not derive from the Myh11 lineage, while no Cdh5-lineage-positive cells were present in the fibroblast cluster. We identified five murine arterial fibroblast subsets in atherosclerotic murine aorta: progenitor fibroblasts, matrix fibroblasts, inflammatory fibroblasts, an EC-like fibroblast subset, detected in both adventitia and plaques, and Col5a3+ fibroblasts, unique to the adventitia. We next studied fibroblast identity, origin, and fate using pseudotime analysis and Pdgfra-CreERT2/tdTomato lineage reporter mice (Pdgfra Lin+). Healthy Pdgfra Lin+ reporter mice showed predominant adventitial tdTomato expression, and infrequent medial and intimal Pdgfra Lin+ cells co-expressing MYH11 and PECAM1, respectively. The Pdgfra Lin+ plaque area increased with diet duration. Pdgfra Lin+ cells largely maintain fibroblast identity in the plaque, while <10% co-express SMC markers (MYH11, SM22α), or contribute to ACTA2+ cap cells. ECs gaining mesenchymal markers are transcriptionally distinct from Cdh5-lineage-negative fibroblasts gaining EC markers. Plaque-resident EC-like fibroblasts displayed a mesenchymal-to-endothelial transition transcriptome, which was induced in human primary fibroblasts in vitro by starvation, and dampened or reversed by IL1B, TGFB1, TGFB3, and oxidized LDL. Cross-species integration showed that all murine plaque fibroblasts were conserved in human atherosclerosis, with one additional subset partially resembling murine subsets, and three human-specific subsets. Importantly, human fibroblast subsets differentially correlated to human plaque traits, with EC-like fibroblasts correlating to plaque instability. CONCLUSION: Our results indicate that 95% of plaque-residing fibroblasts are Myh11 Lin- Plaque fibroblasts have a dual origin, predominantly adventitial Pdgfra Lin+ progenitor fibroblasts, with a minor contribution from medial Pdgfra Lin+  Myh11+ SMCs. Most plaque fibroblasts maintain fibroblast identity. Murine plaque fibroblast subsets were conserved in human atherosclerosis. EC-like fibroblasts are linked to human plaque instability. Intervening in progenitor-to-specific fibroblast transitions could present a new avenue to promote plaque stability in atherosclerosis.

Atherosclerosis↗

PubMed2026

Myeloma engraftment suppresses osteocytic ossification signatures rescued by loading in mice and reveals predictors of patient outcome.

Multiple myeloma (MM) is a malignant plasma cell disease inducing osteolytic lesions by disrupting bone homeostasis, fostering catabolic and suppressing anabolic functions. While the impact on osteoblast generation and function is well documented, alterations of osteocyte function and extracellular matrix (ECM) are not yet fully understood. Thus, using a syngeneic mouse model of MM by injecting MOPC315.BM cells intratibially into BALB/c mice (n = 95), we performed transcriptomic profiling of an osteocyte-enriched population and identified a mechanosensitive matrisomal gene signature, which was disrupted by tumor engraftment. Non-invasive tibial loading restored the expression of 94 ECM-associated genes, including collagens, fibronectin, and aggrecan. Cross-species integration with RNA-seq data from 387 MM patients revealed eight ECM-related genes whose expression correlated with overall survival (VEGFA, BCAN, FGF13, TNFSF8, SDC1, LAMC1, SEMA3A, and CCL2). Four of these genes (Vegfa, Sdc1, Sema3a, Ccl2) were also load-responsive in a murine osteocyte (IDG-SW3 cells) bioreactor model. Our findings indicate that an existing mechanosensitive osteocytic repair program is suppressed by MM cells, which can be reinvigorated via a brief single loading session. It suggests that exercise-based interventions may be beneficial to restore bone mass through endochondral ossification programs in patients with MM.

Bone disease↗

PubMed2025

Evolutionary fingerprints of epithelial-to-mesenchymal transition.

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

Animals↗

PubMed2026

Genome-Wide Identification and Characterization of the TBL Gene Family and Temporal Expression Dynamics During Powdery Mildew Infection in Cucumber (Cucumis sativus).

Cell-wall polysaccharide O-acetylation contributes to cell-wall assembly, organ development, and plant-pathogen interactions, but the cucumber TBL gene family remains poorly characterized. Here, 37 CsTBL genes were identified genome-wide and analyzed using phylogenetic, syntenic, conserved-motif, gene-structure, promoter, protein-structure, Gene Ontology, and transcriptome approaches, followed by RT-qPCR analysis after powdery mildew inoculation. All CsTBL proteins contained the conserved GDS and DxxH motifs, whereas accessory motifs and predicted structural features varied among clades. Intraspecific analysis identified dispersed, WGD/segmental, and tandem duplication categories, and cross-species synteny was more extensive with melon than with Arabidopsis. Homology-derived annotations associated CsTBL genes with cell-wall polysaccharide metabolism, Golgi/endomembrane compartments, and O-acetyltransferase activity, including six genes assigned to xylan O-acetyltransferase-related annotations. Expression profiling revealed tissue- and developmental-stage-dependent patterns, whereas the publicly available powdery mildew RNA-seq dataset provided descriptive temporal expression profiles in Podosphaera xanthii-inoculated samples. Independent RT-qPCR analysis using time-matched mock controls revealed distinct post-inoculation responses among six selected genes. Relative to the corresponding mock controls, CsTBL2 was consistently repressed; CsTBL15 showed transient induction at 1 dpi followed by repression; CsTBL24 exhibited a biphasic response; CsTBL25 was induced at all sampled post-inoculation time points; CsTBL26 showed progressive induction; and CsTBL30 reached its highest observed expression level at 3 dpi. Integrated functional annotation and expression evidence highlighted CsTBL26 as a priority candidate for further functional characterization, while CsTBL24 and CsTBL25 represented fruit-associated candidates with distinct powdery mildew responses; CsTBL30 remained an additional strongly infection-responsive candidate. These findings provide an evolutionary and expression-based framework for the functional characterization of the cucumber TBL gene family.

O-acetylation↗

PubMed2026

Human and mouse adrenal glands are characterized by species-specific steroidogenic states and tissue turnover.

The adult adrenal cortex undergoes constant renewal, yet underlying human-specific mechanisms remain poorly understood. Here we generated single-cell and spatial transcriptomic atlases of adult human and mouse adrenal glands, leveraging single-cell-resolution spatial data and a rare clonal mosaic case for lineage inference. In humans, we identified age-associated zona glomerulosa (ZG) cell states with direct cortisol synthesis capacity and sex-specific differences in inferred cholesterol balance. Cross-species comparison revealed conserved aldosterone-producing ZG but notable divergence in zona fasciculata markers, absence of zona reticularis homologs in mice and differential SHH-WNT4 signaling in proliferating cells. We uncovered human WT1- capsule-to-ZG transition and vascular smooth muscle cell-to-steroidogenic transitions supported by mosaic lineage evidence. We revealed dispersed proliferating cortical SF1+EZH2+ cells throughout the human cortex in contrast with ZG restriction in mice. Taken together, our data expand the centripetal renewal model and establish a comparative framework for human adrenocortical biology.

Animals↗

PubMed2026

Genetic dissection of cardiac iron regulation using transcriptome network analysis and systems genetics in BXD mice.

Cardiac iron homeostasis is essential for myocardial energy metabolism and contractile function, yet the genetic and molecular mechanisms governing iron levels within the heart remain poorly understood. We used a systems genetics approach to dissect the transcriptional regulation of cardiac iron homeostasis. Myocardial iron level varies substantially across BXD strains (40-112 μg/g) and is under heritable genetic control (H2 = 0.38). Elevated cardiac iron is associated with reduced ventricular mass, increased ventricular ectopy, and prolonged atrioventricular conduction in the BXD population. Weighted gene co-expression network analysis of the BXD heart transcriptome identified a co-expression module that was significantly and negatively correlated with cardiac iron levels in both young and old BXD mice and enriched for pathways related to metabolic regulation, cyclic AMP (cAMP) signaling, circadian entrainment, and cardiovascular physiology. The module showed substantial overlap with a curated cardiac iron gene set, and cross-species enrichment analysis confirmed its conservation in human cardiomyopathy differentially expressed genes (enrichment ratio = 1.49; false discovery rate [FDR] = 0.0342). Quantitative trait locus (QTL) mapping of the first principal component of the overlapping module iron genes (n = 38), corroborated by individual gene mapping, identified trans-eQTL hotspots on multiple chromosomes, implicating Fcho2, Gcc2, and Rmdn1 as candidate upstream regulators operating through sequential steps of intracellular iron trafficking. Together, these findings establish a systems-level map of cardiac iron gene regulation, identify candidate genetic regulators, and provide a molecular framework linking disruption of iron-related transcriptional networks to structural and electrical cardiac dysfunction with implications for iron-related heart diseases.

BXD mouse population↗

PubMed2025

Transcriptomic and enzymological evidence for plastid peptidoglycan synthesis in the gymnosperm Picea abies.

It is understood that a cyanobacterium was the progenitor of plastids and that the biosynthesis of cell wall peptidoglycan was lost during chloroplast evolution. However, accumulated data, especially from the moss Physcomitrium patens, suggest that peptidoglycan remains essential for plastid division in some land plants. A fundamental set of peptidoglycan biosynthesis (Mur) genes has been identified in the genomes of these land plants, while many angiosperms no longer encode some core Mur genes, including a bifunctional penicillin-binding protein (PBP). Ten incomplete Mur genes were previously identified in the genome of the gymnosperm Picea abies but these could be pseudogenes or encode proteins that have been repurposed. For instance, mutant albino maize and Arabidopsis seedlings possess a defective UDP-N-acetylmuramoyl-l-alanyl-d-glutamate--2,6-diaminopimelate ligase (MurE), an intact MurE ligase being essential for peptidoglycan synthesis. In this study, we isolated a full set of cDNAs for peptidoglycan biosynthesis from P. abies. GFP fusion proteins with either P. abies (Pa)MurE or PaPBP were detected in chloroplasts. Cross-species complementation assays with PaMurE in Arabidopsis albino MurE mutants and Physcomitrium MurE chloroplast division mutants showed that the gymnosperm MurE completely rescued both mutant phenotypes. Enzymatic assay of recombinant PaMurE proteins revealed they catalyze the same reaction performed by their bacterial MurE homologs. Moreover, the expression of the PaPbp cDNA partially rescued the giant chloroplast phenotype in the moss Pbp knockout line. These results are consistent with the operation of a functional Mur gene set in the Norway spruce genome.

Peptidoglycan↗

PubMed2026

Molecular subgroups of human malignant peripheral nerve sheath tumors are conserved in canines.

Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas of Schwann cell lineage with poor prognosis in both humans and dogs. While rare in humans, MPNSTs occur more frequently in dogs and share histomorphological and clinical features. Recent methylome and transcriptome analyses have identified two molecular subgroups of human MPNST with distinct oncogenic signaling pathways and prognostic implications; however, it remains unclear if these subgroups also exist in canines. Given their higher incidence and biological similarities to human disease, canine MPNSTs represent a promising comparative model to investigate molecular subtypes and evaluate novel therapeutic strategies. To characterize canine MPNST and assess molecular parallels with the human subgroups, we applied laser-capture microdissection (LCM) followed by RNAsequencing to analyze tumor tissue from 20 canine MPNST. Principle component and differential gene expression analyses identified two clearly distinct transcriptional clusters corresponding to spindle cell and epithelioid MPNST variants, respectively. Unsupervised cross-species comparison aligned the two canine clusters with the human G1 and G2 subgroups. Accordingly, one cluster was characterized by SHH pathway activation and increased cell cycle activity, while the other showed non-canonical WNT pathway, Schwann cell-like features and marked macrophage infiltration. Immunohistochemistry further demonstrated loss of H3K27me3, p-ERK activation and β-catenin signaling by IHC in a subset of tumors. These findings support the value of canine MPNST as clinically amenable model for structured assessment of novel therapeutic approaches to benefit patients of both species.

Canine cancer model↗

PubMed2025

A cross-species multi-omics analyze uncovers conserved molecular mechanisms underlying age-related erectile dysfunction.

BACKGROUND: The urgent need for new treatments is driven by the challenging clinical situation of age-related erectile dysfunction (ARED). AIM: To clarify the conserved molecular mechanisms of ARED across species using multi-omics. METHODS: Rat and mouse models with ARED were developed to facilitate the extraction of mRNA and proteins from the corpus cavernosum for high-throughput sequencing. Bioinformatics techniques were employed to analyze differentially expressed genes and to conduct analyses using the Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and protein-protein interaction networks. Verification of the results was carried out using immunofluorescence, hematoxylin-eosin staining, and Masson staining. OUTCOMES: The multi-omics profiles of ARED rats and mice were analyzed and validated across species. RESULTS: In both species, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses of transcriptomic and proteomic data revealed that differentially expressed genes were predominantly enriched in pathways associated with alterations in extracellular matrix composition, downregulation of mitochondrial activity, and disruption of protein homeostasis. Immunofluorescence analysis demonstrated an upregulation of reactive oxygen species expression, coupled with a downregulation of Aldh18a1, collagen, and collagen I expression in the corpus cavernosum of mice and rats with ARED. CLINICAL IMPLICATIONS: To offer a novel approach for enhancing the erectile function in patients with ARED. STRENGTHS AND LIMITATIONS: The primary strength of this study lies in its utilization of cross-species multi-omics sequencing, which has elucidated the conserved molecular mechanisms underlying ARED. However, a significant limitation is the absence of subsequent validation in patients with ARED. CONCLUSIONS: Cross-species multi-omics comparisons present a potentially innovative approach for elucidating the underlying mechanisms and identifying preventive and therapeutic targets for ARED.

aging↗

PubMed2026

Comprehensive identification and evolutionary analysis of the Wnt gene family in bivalves: Insights into the larval development of the noble scallop Chlamys nobilis.

The Wnt gene family regulates fundamental developmental processes in metazoans, but its evolutionary composition and developmental deployment in bivalves remain largely unresolved. Here, we performed a comparative genomic analysis of Wnt genes in 19 bivalve species and examined developmental expression profiles in the noble scallop Chlamys nobilis, with Crassostrea gigas and Chlamys farreri used for cross-species comparison. A total of 235 Wnt genes were identified and assigned to 12 subfamilies. No reliable Wnt3 ortholog was detected in any analyzed bivalve, supporting the view that Wnt3 loss occurred early during lophotrochozoan evolution rather than representing a lineage-specific absence. Most Wnt proteins retained the conserved WNT domain, indicating strong structural conservation, whereas lineage-specific copy-number variation and gene loss were observed among species. C. farreri and C. gigas each retained 12 Wnt genes and lacked Wnt3, whereas C. nobilis lacked Wnt3, Wnt7, and Wnt16. Developmental transcriptome analysis and RT-qPCR revealed clear stage-specific expression patterns. In C. gigas, Wnt2/10/A were highly expressed during earlydevelopment and peaked around the D-shaped larval stage, while Wnt8 and Wnt11 showed distinct stage-specific peaks. By contrast, Wnt1/5/6/9 were more active during later larval development or juvenile formation. These results provide a comparative framework for bivalve Wnt evolution and identify candidate Wnt genes potentially involved in larval development and aquaculture-relevant developmental transitions.

Animals↗