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Results for “comparative transcriptomics”

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PubMed2026

Thyroid hormone deprivation creates an immunological signature in the mouse liver, involving Kupffer cell presentation as the mouse ages.

PURPOSE: Aging is associated with an increased prevalence of chronic liver diseases suggesting impaired immune and metabolic function. In addition, thyroid hormone (TH) impacts liver physiology and TH deprivation or excess negatively affect organ maintenance. However, whether age-dependent consequences of TH alterations are reflected in a liver-specific adaptation is unknown so far. The present study aimed to characterize the impact of TH deprivation or excess on the liver transcriptome during aging. METHODS: Five- and 21-month-old male C57BL/6 mice were exposed either to chronic TH deprivation or to chronic TH excess and compared to control treatment by microarray-based liver transcriptome analysis. RESULTS: Significant roles of both TH state and age became obvious: Bioinformatic analysis of the liver transcriptome data revealed an age-dependent immune signature by chronic TH deprivation, an age-dependent immune and metabolic signature independent of exogenous TH modulation, as well as an age-dependent metabolic signature by chronic TH excess. Published data of single cell transcriptomic atlas characterizing aging tissues in the mouse were compared with our data and revealed Kupffer cell presentation in the immunological signature by TH deprivation during aging. Literature data for four prominent differentially expressed genes, namely C1qb, C3ar1, Ctss, and Msr1, revealed that the complement system, extracellular matrix remodelling, as well as the proinflammatory phenotype of Kupffer cells are altered by TH deprivation during aging. CONCLUSION: In conclusion, our study illuminates the interplay between TH deprivation, aging, and liver transcriptome signatures, highlighting potential implications for immune function and tissue maintenance, particularly through the modulation of Kupffer cell presentation.

Animals↗

PubMed2026

Comparative Multiomics Analysis of Cerebral Organoid-Derived Exosomes during Organoid Maturation.

Cerebral organoids derived from human pluripotent stem cells recapitulate key features of early brain development and provide a physiologically relevant model for neurogenesis. Exosomes secreted by these organoids carry bioactive cargo and offer a noninvasive means to monitor maturation and intercellular communication. We performed comprehensive multiomics profiling of exosomes collected from cerebral organoids at defined developmental stages to evaluate their utility as biomarkers of neuronal differentiation. Metabolomic analysis revealed a progressive decline in amino acids, including glutamic acid, consistent with increased metabolic demand during neurogenesis. Lipidomic and neurosteroid profiling showed dynamic increases in phosphatidylethanolamine and pregnenolone, reflecting synaptic membrane formation and signaling. Transcriptomic and proteomic analyses identified stage-specific neurodevelopmental signatures, with key markers mirroring those of parent organoids. Collectively, cerebral organoid-derived exosomes faithfully reflect organoid maturation and provide a robust platform for tracking in vitro brain development.

Humans↗

PubMed2026

ORFannotate: reproducible coding sequence annotation of transcriptome assemblies.

SUMMARY: Accurate annotation of coding sequences and translational features within transcript models is essential for interpreting assembled transcriptomes and their functional potential. Existing open reading frame (ORF) prediction tools typically operate on transcript FASTA files and do not reintegrate coding sequence (CDS) information back into transcript models, limiting their utility in long-read sequencing workflows where GTF/GFF annotations are the primary output. We present ORFannotate, a lightweight, GTF-native Python command-line tool that predicts ORFs from transcript annotations and reinserts precise, exon-aware CDS and UTR features into the original GTF/GFF file. In addition, ORFannotate provides biologically informative translational context by annotating Kozak sequence strength, detecting non-overlapping upstream ORFs (uORFs) with coding probabilities, characterising 5' and 3' untranslated regions (UTRs), and predicting nonsense-mediated decay (NMD) susceptibility. All annotations are consolidated in a transcript-level summary to support downstream analysis. By generating GTF files with accurate CDS annotations, ORFannotate facilitates reproducible analysis of both long- and short-read transcriptomes and integrates seamlessly with visualization tools, genome browsers, and comparative transcript analysis workflows. ORFannotate is fast, scalable and provides a practical solution for transcriptome annotation beyond coding potential prediction alone. AVAILABILITY AND IMPLEMENTATION: ORFannotate is implemented in Python and freely available under the GNU General Public License v3 (GPL-3.0) at: https://github.com/egustavsson/ORFannotate (DOI: https://doi.org/10.5281/zenodo.16812866).

Open Reading Frames↗

PubMed2026

Insights into the mechanism of enhanced tetramethylpyrazine production in dehulled adlay fermented by Bacillus subtilis BJ3-2.

Tetramethylpyrazine (TTMP) is a vital bioactive alkaloid and characteristic flavor compound in fermented foods. Our previous study found that fermentation of adlay by Bacillus subtilis BJ3-2 efficiently accumulates TTMP, whereas the underlying high-yield mechanism remains unclear. This study investigated the fermentation characteristics, gene transcription and protein expression of B. subtilis BJ3-2 in dehulled adlay (BDA) and soybean (BSB), respectively, and elucidated the mechanism responsible for high-yield TTMP production. The results showed that glutamate, leucine and phenylalanine were major free amino acids in BDA. The TTMP yield in BDA at 48 h (6.11 mg/g dry weight) was 360-fold higher than that in BSB. Transcriptomic and proteomic analysis demonstrated that compared with the soybean substrate, dehulled adlay substrate significantly up-regulated the expression of alsSD and ilvBH genes and their encoding proteins in B. subtilis BJ3-2, which were involved in C5-branched dibasic acid metabolism, 2-oxocarboxylic acid metabolism, and valine, leucine and isoleucine biosynthesis. Meanwhile, acetoin degradation was inhibited by down-regulating acetoin dehydrogenase complex (acoABCL) in citrate cycle, glycolysis/gluconeogenesis and carbon metabolism. Additionally, nitrogen metabolism pathway was transcriptionally enhanced to guarantee sufficient ammonium supply. Notably, protein-protein interaction and molecular docking analyses revealed that acetohydroxyacid synthase (ilvBH) interacted tightly with α-acetolactate decarboxylase (alsD), potentially forming a metabolic channel for acetoin synthesis. In conclusion, the efficient synthesis of TTMP in BDA was primarily attributed to the high synthesis and low degradation of acetoin, and the moderate synthesis of ammonium/ammonia. This study provided a theoretical basis for the targeted and efficient biosynthesis of TTMP.

Bacillus subtilis↗

PubMed2025

Synthetic allopolyploidy unveils hybridization-driven transcriptional reprogramming underlying thermal adaptation in Cucumis.

Both heterosis (hybrid vigor) resulting from hybridization and genetic plasticity conferred by whole-genome duplication (WGD) are recognized as drivers of evolutionary success and ecological adaptation in plants. Allopolyploids, which combine both hybridization and WGD, are widespread in both natural and agricultural settings and often exhibit superior performance. However, the relative contributions of these two elements to the success of allopolyploids remain poorly understood. Here, we employed an experimentally reconstructed allotetraploid Cucumis species (C. × hytivus, 2n = 4x = 38) and its diploid interspecific hybrid progenitor (allodiploid, 2n = 2x = 19) to decouple and investigate the distinct and combined contributions of hybridization and whole-genome doubling to immediate genetic and phenotypic consequences of allopolyploid formation under environmental stress. Both C. × hytivus and the allodiploid exhibited superior heat tolerance compared with the parental species with significantly higher semi-lethal temperature and enhanced physiological acclimation capacity. While the allodiploid and allotetraploid retain transcriptomic features where differences persist (e.g., WGCNA modules), comparative analysis of the 15,680 homoeologous gene pairs in the allodiploid and allotetraploid under heat stress (45°C) versus control conditions (28°C) revealed conserved heat-responsive transcriptional plasticity, suggesting that enhanced thermotolerance in C. × hytivus is presented as consequences arising dominantly after interspecific hybridization. This study provides mechanistic insights into allopolyploid adaptation through experimental reconstruction of allopolyploid genomes, demonstrating that hybridization initiates key transcriptional and physiological advantages under stress, subsequent WGD stabilizes these adaptations and contributes to the full phenotypic realization. This work decouples the roles of interspecific hybridization and WGD and proposes a synthetic biology approach for developing climate-resilient crops.

Hybridization, Genetic↗

PubMed2025

Coordinated regulation of glutathione S-transferases confers metabolic flexibility in multi-insecticide-resistant Frankliniella occidentalis (Pergande).

INTRODUCTION: The evolution of multi-insecticide resistance in insect pests threatens global food security. Although glutathione S-transferases (GSTs) are implicated in detoxification, the coordinated mechanism by which specific gene subfamilies interact to confer broad-spectrum resistance remains inadequately characterized. OBJECTIVE: To dissect the functional allocation and cooperation of GST subfamilies in multi-insecticide-resistant strains of Frankliniella occidentalis. METHODS: We integrated comparative genomics (20 GST genes cloned), transcriptomics (qRT-PCR), RNAi-mediated silencing, molecular docking (AutoDock Vina), and in vitro metabolism assays (UPLC-MS/MS) across susceptible and resistant thrips strains. RESULTS: The two resistant strains (NIL-R and FS-R) exhibited moderate to high resistance to five insecticides (chlorfenapyr, emamectin benzoate, spinetoram, spinosad, and thiamethoxam), accompanied by significantly elevated GSTs activity. Phylogenetic analysis indicates that GSTs include 10 conserved delta and 7 diverse sigma members. The sigma subfamily has undergone a marked expansion due to gene duplication. Delta (FoGSTd1, d4, and d9) and sigma (FoGSTs1, s2, and s6) genes were significantly up-regulated in the resistant strains. RNAi showed specialized functional allocation among GSTs: delta GSTs mediated resistance to spinosad and chlorfenapyr, sigma GSTs were responsible for thiamethoxam resistance, and notably, cooperation between these subfamilies contributed to resistance against emamectin benzoate and spinetoram. Molecular docking and in vitro metabolism assays of FoGSTd9 and FoGSTs1 proteins further supported the functional allocation and cooperative roles of GST subfamilies. CONCLUSION: Our results indicate that F. occidentalis may coordinate GST subfamilies to achieve metabolic flexibility in response to multi-insecticide pressure. This survival strategy, mediated by mechanistic functional allocation and cooperative interactions among subfamilies, may contribute to energy conservation and reduced adaptive costs. Disruption of this coordinated mechanism represents a potential approach for overcoming resistance in agricultural pest populations.

Animals↗

PubMed2024

Spatiotemporal single-cell roadmap of human skin wound healing.

Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell multi-omics analyses on human skin wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations.

Humans↗

PubMed2025

Proteomic snapshot of pattern triggered immunity in the Arabidopsis leaf apoplast.

The apoplast is a critical interface in plant-pathogen interactions, particularly in the context of pattern-triggered immunity (PTI), which is initiated by recognition of microbe-associated molecular patterns. Our study characterizes the proteomic profile of the Arabidopsis apoplast during PTI induced by flg22, a 22-amino-acid bacterial flagellin epitope, to elucidate the output of PTI. Apoplastic washing fluid was extracted with minimal cytoplasmic contamination for liquid chromatography-tandem mass spectrometry analysis. By comparing our data to publicly available transcriptome profiles of flg22 treatment from 1 to 18 h, we observed that several highly abundant proteins exhibit relatively unchanged gene expression across all time points. We also observed topological bias in peptide recovery of 19 enriched receptor-like kinases with peptides predominantly recovered from their ectodomains. Notably, tetraspanin 8, an exosome marker, was enriched in PTI samples. We additionally confirmed increased concentrations of exosomes during PTI. This study enhances our understanding of the proteomic changes in the apoplast during plant immune responses and lays the groundwork for future investigations into the molecular mechanisms of plant defense under recognition of pathogen molecular patterns.

Arabidopsis↗

PubMed2026

Genetic evidence prioritizes circulating proteins for heart failure beyond shared BMI-related genetic liability.

BACKGROUND: Heart failure (HF) and body mass index (BMI) share substantial genetic architecture, which may lead genetically informed target discovery to preferentially identify adiposity-related pathways. We sought to identify circulating proteins associated with HF beyond this shared genetic component. METHODS: We applied GWAS-by-subtraction to overall HF, nonischemic HF, and nonischemic HF with reduced or preserved ejection fraction to derive BMI-related and BMI-subtracted HF components. We then performed proteome-wide cis-pQTL Mendelian randomization and colocalization using four independent proteomic cohorts, followed by tissue-specific eQTL colocalization, cardiac transcriptomic annotation, and druggability assessment. RESULTS: Compared with the original HF phenotypes, the BMI-subtracted components showed attenuated genetic correlations with BMI (0.045-0.147) while retaining 28 independent loci for overall HF and nine for nonischemic HF. Across 19,930 protein-HF tests, 11 associations involving nine proteins were prioritized by the Mendelian randomization and colocalization analyses. For example, a 1-SD increase in genetically predicted CELSR2 abundance was associated with lower overall HF risk (odds ratio, 0.96 [95% CI, 0.94-0.98]; P=8.6×10-7), whereas a 1-SD increase in genetically predicted CSF3 abundance was associated with higher nonischemic HF risk (odds ratio, 1.32 [95% CI, 1.18-1.48]; P=2.0×10-6). CELSR2 and TMEM106B colocalized with cis-eQTLs in failing left ventricular myocardium, and DAG1 showed cardiomyocyte enrichment with concordant downregulation in failing hearts. CONCLUSIONS: We identified nine circulating proteins associated with HF beyond the genetic component shared with BMI. These findings extend the range of genetically supported pathways implicated in HF and nominate candidate proteins for further mechanistic and therapeutic investigation.

Genetics↗

PubMed2026

Transcriptomic analysis provides molecular insights into the innate immune defense of Mactra veneriformis against Vibrio alginolyticus infection.

Mactra veneriformis is an economically important bivalve mollusc in China, but its aquaculture is frequently threatened by Vibrio infections, particularly Vibrio alginolyticus. To investigate the molecular immune response of M. veneriformis to V. alginolyticus, we performed RNA-seq analysis of hepatopancreatic tissues collected at 48 h post-infection, the peak mortality time point, with PBS-injected individuals used as controls. Infection with V. alginolyticus caused severe histopathological damage in the hepatopancreas and resulted in a cumulative mortality of 53.3% over 14 d, compared with 3.3% in the control group. Transcriptomic analysis identified 2623 differentially expressed genes (DEGs), including 1585 significantly up-regulated genes and 1038 down-regulated genes. KEGG enrichment analysis demonstrated that DEGs were significantly enriched in immune related and metabolism pathways, including the JAK-STAT signaling pathway, RIG-I-like receptor (RLR) signaling pathway, and cytochrome P450 (CYP450) signaling pathway. Collectively, these findings revealed candidate immune related genes (tlr3, tlr5, myd88, nfkb1, il-17d, and ifi44l), a putative TLR-MyD88-NF-κB signaling axis, and KEGG signaling pathways, including JAK-STAT, RLR and CYP450, that may be involved in the innate immune response of M. veneriformis to V. alginolyticus infection. These results provide a transcriptomic basis for understanding host-pathogen interactions in this species and highlight candidate genes and pathways for future functional validation and potential application in disease-resistance breeding.

Animals↗

PubMed2026

The molecular similarity landscape of preclinical cancer models to patient tumors.

Selecting appropriate preclinical models is fundamental for translational oncology, yet a large-scale, multi-omic quantitative comparison of their similarity to primary human tumors is lacking. To address this, we integrated transcriptomic, proteomic, and genomic profiles from over 10,000 primary tumors from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), alongside 4,000 preclinical models. Using a robust computational framework, we revealed a clear hierarchy of transcriptomic and proteomic similarity to patient tumors: with patient-dervied xenografts (PDXs) having greater transcriptomic and proteomic similarity to patient tumors (>) compared with patient-derived organoids (PDOs), which are equal in hierarchy to that of PDX-dervied organoids (PDXOs) > cell lines. We also quantified high molecular conservation (Pearson correlation coefficient = 0.96) across paired in vitro to in vivo platform (organoids to PDX) transitions. Furthermore, genomic analysis demonstrated that whole-exome sequencing (WES) outperforms RNA-seq in detecting DNA variants, and it identified a clonal complexity hierarchy (cell lines > PDXOs > PDXs > PDOs) reflecting the effect of passaging history on intratumor heterogeneity. Ultimately, this study delivers a comprehensive quantitative benchmark, establishing a population-level hierarchy of molecular similarity between preclinical models and primary tumors and providing a data-driven reference for model selection. These findings offer a data-driven framework for selecting models that balance biological representativeness with experimental practicality.

Humans↗

PubMed2026

Histopathological evaluation of RPL5 expression in triple-negative breast cancer: an integrated immunohistochemical and transcriptomic study.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high invasiveness, limited therapeutic options, and unfavorable clinical outcomes. Ribosomal protein L5 (RPL5), a component of the large ribosomal subunit, has been implicated in ribosome biogenesis, translational regulation, and p53-associated cellular processes. This study investigated the immunohistochemical expression pattern of RPL5 in TNBC tissues and explored its potential biological significance through integrated transcriptomic analyses. Tumor tissues from 37 patients with TNBC and 7 adjacent non-tumorous breast tissues were collected from the Affiliated Tumor Hospital of Xinjiang Medical University between December 2017 and December 2023. RPL5 protein expression was evaluated by immunohistochemistry, and its association with clinicopathological characteristics was analyzed. Public transcriptomic datasets from TCGA-BRCA and GEO were further used to validate RPL5 expression patterns in TNBC. Co-expression analysis and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate potential biological functions and signaling pathways associated with RPL5. Immunohistochemical analysis demonstrated significantly lower RPL5 protein expression in TNBC tissues compared with adjacent normal breast tissues (p=0.001). In contrast, transcriptomic analyses revealed significantly higher RPL5 expression in TNBC compared with non-TNBC breast cancer subtypes (p<0.001). No significant associations were observed between RPL5 expression and clinicopathological parameters, including age, tumor size, menopausal status, TNM stage, histological grade, or lymph node metastasis (all p>0.05). Survival analysis showed no significant difference in overall survival between patients with high and low RPL5 expression. Functional enrichment analyses indicated that RPL5-related genes were predominantly involved in ribosome biogenesis, translational regulation, and p53-related signaling pathways. These findings suggest that abnormal RPL5 expression may be associated with TNBC biology through ribosome-related programs, although causal roles require functional validation. RPL5 may represent a potential histopathological and molecular indicator associated with TNBC biology, although its precise functional role requires further experimental validation.

Humans↗

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↗

PubMed2025

Defining the networks that connect RNase III and RNase J-mediated regulation of primary and specialized metabolism in Streptomyces venezuelae.

UNLABELLED: RNA metabolism involves coordinating RNA synthesis with RNA processing and degradation. Ribonucleases play fundamental roles within the cell, contributing to the cleavage, modification, and degradation of RNA molecules, with these actions ensuring appropriate gene regulation and cellular homeostasis. Here, we employed RNA sequencing to explore the impact of RNase III and RNase J on the transcriptome of Streptomyces venezuelae. Differential expression analysis comparing wild-type and RNase mutant strains at distinct developmental stages revealed significant changes in transcript abundance, particularly in pathways related to multicellular development, nutrient acquisition, and specialized metabolism. Both RNase mutants exhibited dysregulation of the BldD regulon, including altered expression of many cyclic-di-GMP-associated enzymes. We also observed precocious chloramphenicol production in these RNase mutants and found that in the RNase III mutant, this was associated with PhoP-mediated regulation. We further found that RNase III directly targeted members of the PhoP regulon, suggesting a link between RNA metabolism and a regulator that bridges primary and specialized metabolism. We connected RNase J function with translation through the observation that RNase J directly targets multiple ribosomal protein transcripts for degradation. These findings establish distinct but complementary roles for RNase III and RNase J in coordinating the gene expression dynamics critical for S. venezuelae development and specialized metabolism. IMPORTANCE: RNA processing and metabolism are mediated by ribonucleases and are fundamental processes in all cells. In the morphologically complex and metabolically sophisticated Streptomyces bacteria, RNase III and RNase J influence both development and metabolism through poorly understood mechanisms. Here, we show that both ribonucleases are required for the proper expression of the BldD developmental pathway and contribute to the control of chloramphenicol production, with an interesting connection to phosphate regulation for RNase III. Additionally, we show that both RNases have the potential to impact translation through distinct mechanisms and can function cooperatively in degrading specific transcripts. This study advances our understanding of RNases in Streptomyces biology by providing insight into distinct contributions made by these enzymes and the intriguing interplay between them.

Streptomyces↗

PubMed2026

Proteomic analysis of pancreatic endocrine cells by mechanistic single-cell isolation identifies membrane pathways.

To better understand diabetes and normoglycemia, pancreatic islet biology requires a precise molecular understanding of islet cell types at both the transcriptomic and proteomic levels. While transcriptomic analyses are well established, comprehensive proteomic characterization has been lacking, limiting our knowledge of islet molecular complexity. Here we introduce a nonenzymatic, mechanistic single-cell isolation technology using laser microdissection (LMD7), facilitating proteomic and transcriptomic analysis of physically isolated α-, β- and δ-cells from fresh-frozen, unfixed pancreatic tissue. This mechanistic approach avoids enzymatic digestion and chemical fixation, preserving the cells' native molecular state before processing. Given the limited existing proteomic data, we supplemented our findings with transcriptomic analysis generated using the same method and compared our results with data from enzymatically isolated cells, obtained by fluorescence-activated cell sorting and compiled by others. Our analysis revealed that enzymatic digestion alters gene expression patterns, particularly those of membrane-associated proteins, underscoring the impact of isolation techniques on biological outcomes. We identified cell-type-specific proteins typically underrepresented in pancreatic single-cell transcriptomic datasets. β-cells exhibited enrichment in vesicle trafficking proteins, α-cells displayed distinct calcium-dependent action potential machinery and δ-cells showed elevated expression of focal adhesion-related proteins. In addition, we report an inverse molecular relationship between β- and δ-cells, potentially driven by transcriptional regulators such as Mlxipl. By establishing robust molecular profiles directly from intact pancreatic tissue, this work provides a reference point for future pathological comparisons, offering a framework to investigate how diabetes and other endocrine disorders reshape islet cell biology.

Journal Article↗

PubMed2026

Deciphering novel targets in salivary gland pleomorphic adenoma by integrating plasma proteomics and parotid transcriptomics analyses.

BACKGROUND/PURPOSE: Pleomorphic adenoma (PA) is the most common salivary gland benign tumor, with its molecular drivers elusive due to a lack of experimental models. This study aimed to decipher novel targets in PA by systematically integrating plasma protein quantitative trait loci (pQTL)-based Mendelian randomization (MR) with multi-omics profiling of parotid gland tissues. MATERIALS AND METHODS: We performed two-sample MR using 5450 plasma pQTLs and genome-wide association study summary for benign or broader salivary gland diseases from FinnGen consortium. Bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) comparing PA to normal tissue were used for transcriptomic validation. Immunohistochemistry (IHC) was applied for protein-level validation in human PA, adenoid cystic carcinoma (ACC), and murine inflammatory lesions. RESULTS: MR identified 12 plasma proteins associated with benign salivary gland tumor risk. Transmembrane serine protease 6 (TMPRSS6) was the only protein significantly risk-increasing for both benign and broader salivary gland diseases. Strikingly, mitogen-activated protein kinase kinase 4 (MAP2K4) showed opposite MR effects between benign and all-lesion outcomes. Bulk RNA-seq showed limited concordance with MR findings, while scRNA-seq revealed a unique plastic epithelium and partially validated candidates at cellular resolution. Critically, IHC confirmed MAP2K4 protein overexpression specifically in human PA, but not in ACC or inflammatory lesions, while TMPRSS6 was downregulated in established pathologies despite its genetic risk association. CONCLUSION: By integrating plasma proteome-based causal inference with parotid tissue multi-omics, this study unveils MAP2K4 as a potential PA-specific driver. This integrative framework provides novel, context-specific targets for further functional investigation in salivary gland tumorigenesis.

Gene expression profiling↗

PubMed2025

Efficacy of Repeated Administration of Cultured Human CD34+ Cells Against Streptozotocin-Induced Diabetic Nephropathy in Rats.

To date, no clinical trial has investigated the potential of CD34+ cells to treat diabetic nephropathy. This study examined the efficacy of human CD34+ cells against diabetic nephropathy in rats. Rats were administered streptozotocin (STZ) intraperitoneally and divided into three groups: normal control, STZ control, and STZ plus cell therapy. The STZ-plus-cell-therapy group was administered human umbilical cord blood-derived CD34+ cells weekly for three weeks. At eight weeks, the rats' renal function, pathology, and transcriptome profiles were assessed. Although blood glucose levels did not differ between the STZ-administered groups, urinary albumin excretion was significantly lower at 6 weeks in the STZ-plus-cell-therapy group than in the STZ control group (p < 0.001). Serum creatinine levels tended to be higher in the STZ control group and lower in the STZ-plus-cell-therapy group. Cell therapy significantly improved mesangial expansion, interstitial fibrosis, peritubular capillary rarefaction, and glomerular macrophage infiltration compared with the STZ control (p < 0.0001). Kidney transcriptomics revealed significant upregulation of genes related to M2 macrophage markers, cell homing, and angiogenesis in the STZ-plus-cell-therapy group. In rats with STZ-induced diabetic nephropathy, human CD34+ cells ameliorated renal injury through their anti-inflammatory and pro-angiogenic effects.

Animals↗

PubMed2026

Transcriptomic Insights into Acupuncture Mechanisms in Protecting Ovarian Function in Mice with Premature Ovarian Insufficiency.

OBJECTIVE: To explore the molecular mechanisms underlying the protective effect of acupuncture on ovarian function in mice with cyclophosphamide-induced premature ovarian insufficiency (POI) via transcriptomic analysis. METHODS: Twenty female C57BL/6 mice were divided into 4 groups: control, model, acupuncture, and non-meridian/non-acupoint (NOMA). POI was induced in the model, acupuncture, and non-meridian/non-acupoint groups via cyclophosphamide injection. The acupuncture group received acupuncture at Guanyuan (CV 4), bilateral Guilai (ST 29), and Sanyinjiao (SP 6) for 3 weeks. After the intervention, ovarian tissue weight and ovarian coefficient were calculated, serum levels of key reproductive hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) were detected, and ovarian histopathological changes were observed to evaluate ovarian function. Transcriptome sequencing was performed to identify differentially expressed genes (DEGs), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to explore key functional terms and signaling pathways. Western blot was finally applied to validate the expression of core proteins related to mitochondrial function, endoplasmic reticulum stress and inflammatory pathways. RESULTS: The model group showed reduced ovarian weight and elevated FSH levels. The acupuncture group exhibited significantly higher ovarian weight and coefficient, lower FSH levels, and increased E2 and AMH levels compared to the model group (all P<0.01). Transcriptomic analysis revealed 4,021 DEGs between groups. GO and KEGG analyses revealed that these DEGs were mainly involved in oocyte development, steroid hormone synthesis, and pathways related to mitochondrial function, endoplasmic reticulum stress, and inflammatory signaling. Western blot analysis showed that acupuncture partially restored mitochondrial function markers cytochrome c oxidase subunit IV and NADH dehydrogenase 1 beta subcomplex subunit 8 and reduced endoplasmic reticulum stress markers (glucose-regulated protein 78 and Calnexin, P<0.01). It also downregulated pro-inflammatory proteins (IL-17R, IL-17A, NF-κB p65, p-NF-κB p65, ERK1/2, and p-ERK1/2) and upregulated proteins related to metabolic homeostasis (peroxisome proliferator-activated receptor γ, receptor-interacting protein 140, nicotinamide phosphoribosyltransferase, and sirtuin 1, P<0.01). CONCLUSION: Acupuncture effectively alleviates cyclophosphamide-induced POI in mice, improves ovarian function and follicular quality by regulating cellular functions and inflammatory pathways, suggesting a novel therapeutic approach for POI.

acupuncture↗