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Results for “transcriptomic profiling”

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PubMed2025

CAFs activated by YAP1 upregulate cancer matrix stiffness to mediate hepatocellular carcinoma progression.

BACKGROUND: The stiffness of the matrix is closely related to the progression of hepatocellular carcinoma (HCC). Although direct targeting of stromal rigidity in HCC remains a clinical challenge, cancer-associated fibroblasts (CAFs) are considered key contributors to this process. Given the heterogeneity of CAFs, this study explored the relationship between specific CAF subsets and liver cancer matrix stiffness, aiming to identify novel therapeutic targets for HCC patients. METHODS: Single-cell sequencing datasets were leveraged to identify cell types within liver cancer and characterize the transcriptomic profiles of CAFs. Prognostic analysis, utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) liver cancer datasets, assessed the correlation between matrix stiffness-related genes and HCC patient outcomes. Pseudo-time analysis was applied to trace the developmental trajectories of CAFs. By calculating intercellular communication probabilities and analyzing transcription factor activity, the functions and interactions of different CAF subsets were elucidated. Gene Ontology (GO) analysis was used to explore the functional roles of CAFs in distinct Yes-associated protein 1 (YAP1) groups. Finally, cellular experiments and animal experiments were further conducted to validate the hypotheses of this study. RESULTS: This study identified CAF subpopulations based on single-cell sequencing data and analyzed transcriptional changes within these subpopulations. Key findings include the identification of collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and lysyloxidase (LOX) as pivotal node genes during CAF development. Moreover, the expression of matrix stiffness-related genes was inversely correlated with the prognosis of HCC patients. Notably, the YAP1-positive CAF subpopulation emerged as the primary contributor to matrix stiffness in liver cancer. This subpopulation upregulates the expression of matrix stiffness-related genes and promotes tumor progression by activating signaling pathways such as autophagy and GTPase activity regulation. Cellular experiments and animal studies further validated this conclusion. CONCLUSION: This single-cell analysis uncovered the functional roles of CAFs in liver cancer. The YAP1-positive CAF subpopulation, in particular, was shown to contribute to matrix stiffness by upregulating the expression of relevant genes and promoting tumor progression through the activation of specific signaling pathways.

Carcinoma, Hepatocellular↗

PubMed2026

Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications.

BACKGROUND: The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) pathway acts as a pivotal innate immune sensor that detects cytosolic DNA and links genomic instability to antitumor immune activation. Therapeutic activation of this pathway has garnered substantial interest as a strategy to enhance cancer immunotherapy by promoting dendritic cell maturation, augmenting antigen presentation, and facilitating cytotoxic lymphocyte infiltration. However, the functional outcomes of cGAS–STING signaling are highly context dependent and influenced by both cell type and tumor microenvironmental (TME) conditions. MAIN BODY: Recent advances in single-cell and spatial transcriptomic profiling have revealed profound heterogeneity in cGAS–STING activation across distinct cellular and regional compartments within tumors. Acute and spatially restricted activation of the pathway can elicit potent antitumor immune responses, whereas chronic or dysregulated signaling may promote immune tolerance and tumor progression. Moreover, metabolic stress, epigenetic silencing, and microenvironmental immunosuppressive factors such as TGF-β and IL-10 can further modulate STING activity, leading to resistance to immunotherapy. Current translational efforts focus on next-generation STING agonists, nanoparticle-based delivery systems, and rational combination strategies with immune checkpoint blockade and metabolic modulators to overcome tumor-intrinsic resistance and minimize systemic toxicity. CONCLUSIONS: Understanding the cell-type-specific and spatial dynamics of cGAS–STING signaling is crucial for the rational design of precision immunotherapies. Future research should emphasize context-dependent modulation of STING activity to maximize therapeutic benefit while limiting adverse effects. Integrating multi-omics technologies and spatially guided drug delivery may ultimately enable personalized modulation of the cGAS–STING axis, transforming it into a clinically effective and safe strategy for cancer immunotherapy.

Humans↗

PubMed2026

Enhancing the fiber degradation efficiency in dairy cattle rumen through engineered bacterial communities.

BACKGROUND: The rumen functions as an anaerobic fermentation chamber, housing microorganisms with cellulolytic and proteolytic capabilities that facilitate feed utilization. Fiber-degrading bacteria possess the capability to enhance the productivity of cellulolytic feed. The application of omics technologies has greatly improved our understanding of the rumen microbiome. Determining microbial composition and functional patterns in the rumen does not equate to a comprehensive exploration of rumen microbial resources and their mechanisms of action. This study seeks to integrate high throughput 16S rRNA data with information on culturomics, cellulolytic activities, nutrition, and synthetic microbial communities (SynCom) engineering. The objective is to evaluate the relationship between rumen microbial activity and fiber utilization efficiency in cattle, ultimately aiming to develop a more powerful intervention strategy for the ruminant industry. RESULTS: The enrichment culture with various carbon sources led to significant alterations in the composition and structure of rumen microbiota, particularly enhancing those associated with carbohydrate metabolism. Employing the culturomics methodology, 896 strains from 78 species (including 8 novel species) were isolated, resulting in a 10.1% isolation rate relative to the rumen bacterial community. Among them, 35 strains demonstrated boosted cellulose-degrading capability on plates, while 25 exhibited the ability to degrade hemicellulose as well. SynComs of these candidates were prepared based on the ratio observed in rumen microbiota exhibiting high cellulolytic performance. SynCom 3 improved the neutral detergent fiber degradation (NDFD) by 20.39% averagely. Additionally, both in vitro and in situ assessments indicated that the optimization of dose/strain in SynCom 3 significantly improved the in vitro NDFD by 20.56% and increased the in situ NDFD by 7.81%, along with the acidic detergent fiber (ADF, + 11.47%). Genomic analysis revealed that the SynCom 3 functioned well in fiber degradation through the synergistic action of key carbohydrate-active enzymes. CONCLUSIONS: This study strengthens rumen microbiome research by integrating omics and SynCom engineering within a microbiota-bacteria-enzymes-genes framework, revealing the significance of enzymatic synergy in carbohydrate metabolism. The findings establish a framework for utilizing low-abundance microbes and engineering functional consortia, which are crucial for improving ruminant feed utilization and biomass conversion. Future research should investigate the transcriptomic profiles and the metabolic cross-feeding mechanisms of fiber-degrading strains in the rumen. Video Abstract.

Animals↗

PubMed2026

The Landmark Series: Mutation-Based Therapy of Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited long-term survival despite advances in surgery and systemic therapy. PATIENTS: The population of interest comprises patients with PDAC characterized by targetable molecular alterations and biologically distinct transcriptomic subtypes. METHODS: We performed a narrative review of landmark and contemporary clinical trials, translational studies, and emerging molecular-classification platforms relevant to precision oncology in PDAC. RESULTS: Growing understanding of PDAC molecular biology has identified putative genetic mutations, including homologous recombination repair deficiency, mismatch repair deficiency, and mutated KRAS, enabling the development of targeted therapies and precision treatment strategies. Concurrently, transcriptomic profiling has revealed biologically distinct molecular subtypes associated with differences in prognosis and therapeutic response. Emerging tools such as molecular classifiers, deep learning models, and multiomic platforms may further refine patient selection and treatment personalization. CONCLUSIONS: This review highlights contemporary efforts of novel targeted therapies, ongoing advances in molecular subtyping, and the evolving role of precision oncology in improving outcomes for patients with PDAC.

Genomic alterations↗

PubMed2026

Outbreaks of fluconazole-resistant Candida parapsilosis are driven by low-biofilm-producing isolates that emerge under host selection.

Candida parapsilosis is a major human fungal pathogen, with recent global outbreaks driven by fluconazole-resistant (FLCR-Cp) isolates that are difficult to eradicate and associated with poor clinical outcomes. However, the microbial traits enabling persistence of these outbreak lineages remain poorly defined. Here, we show that FLCR-Cp isolates responsible for prolonged, multi-country outbreaks consistently exhibit a striking low-biofilm-producing (LBP) phenotype. Contrary to the prevailing view that robust biofilm formation promotes persistence, LBP strains displayed enhanced stress tolerance, increased cell wall masking, and reduced immune recognition. These traits conferred resistance to neutrophil and macrophage killing and enhanced survival in immune cell-rich organs during systemic infection. Genome-wide transcriptomic profiling revealed extensive metabolic and regulatory rewiring in LBP strains. Whole-genome sequencing (WGS) of a global isolate collection further demonstrated that the LBP phenotype has emerged independently multiple times, supporting convergent evolution under host selection. Functional genomic analyses suggest that biofilm attenuation arises through multigenic changes, and disruption of key biofilm-associated transcriptional regulators enhanced fitness during immune interactions. Together, our findings overturn the assumption that robust biofilm formation drives outbreak persistence and instead identify biofilm attenuation as an adaptive tradeoff that promotes immune evasion and long-term survival. These results redefine our understanding of C. parapsilosis adaptation during healthcare-associated outbreaks and shift attention toward host-driven evolutionary processes than environmental persistence alone.

Biofilms↗

PubMed2025

A targeted CRISPR screen identifies ETS1 as a regulator of HIV-1 latency.

Human Immunodeficiency virus (HIV) infection is regulated by a wide array of host cell factors that combine to influence viral transcription and latency. To understand the complex relationship between the host cell and HIV-1 latency, we performed a lentiviral CRISPR screen that targeted a set of host cell genes whose expression or activity correlates with HIV-1 expression. We further investigated one of the identified factors - the transcription factor ETS1, and found that it is required for maintenance of HIV-1 latency in both latently infected cell lines and in a primary CD4 T cell latency model. Interestingly, ETS1 played divergent roles in actively infected and latently infected CD4 T cells, with knockout of ETS1 leading to reduced HIV-1 expression in actively infected cells, but increased HIV-1 expression in latently infected cells, indicating that ETS1 can play both a positive and negative role in HIV-1 expression. CRISPR/Cas9 knockout of ETS1 in CD4 T cells from ART-suppressed people with HIV-1 (PWH) confirmed that ETS1 maintains transcriptional repression of the clinical HIV-1 reservoir. Transcriptomic profiling of ETS1-depleted cells from PWH identified a set of host cell pathways involved in viral transcription that are controlled by ETS1 in resting CD4 T cells. In particular, we observed that ETS1 knockout increased expression of the long non-coding RNA MALAT1 that has been previously identified as a positive regulator of HIV-1 expression. Furthermore, the impact of ETS1 depletion on HIV-1 expression in latently infected cells was partially dependent on MALAT1. Additionally, we demonstrate that ETS1 knockout resulted in enhanced abundance of activating modifications (H3K9Ac, H3K27Ac, H3K4me3) on histones located at the HIV-1 long terminal repeat (LTR), indicating that ETS1 regulates the activity of chromatin-targeting complexes at the HIV-1 LTR. Overall, these data demonstrate that ETS1 is an important regulator of HIV-1 latency that impacts HIV-1 expression through repressing MALAT1 expression and by regulating modification of proviral histones.

Proto-Oncogene Protein c-ets-1↗

PubMed2006

ppGalNAc-T13: a new molecular marker of bone marrow involvement in neuroblastoma.

BACKGROUND: To identify new molecular markers of bone marrow dissemination in human neuroblastoma (NB), we studied the transcriptome profiles of malignant neuroblasts established from the human MYCN-amplified IGR-N-91 model. METHODS: This experimental model includes human neuroblastoma cells derived from a subcutaneous stage 4 disease, myocardium (Myoc) and bone marrow (BM) metastatic cells. RESULTS: Gene expression profiles obtained with Agilent oligo microarrays revealed a set of 107 differentially expressed genes in the metastatic neuroblasts. This set included up-regulated genes involved in chemoresistance, cell motility, neuronal structure/signaling, and the recently characterized GALNT13 gene encoding a glycosyltransferase that initiates mucin-type O-glycosylation. Because the glycosylation process is involved in the progression of primary tumor to metastatic disease, we investigated whether the most strongly up-regulated gene, GALNT13, might be a marker of bone marrow involvement in stage 4 NB patients. Importantly, in the BM of healthy adults no GALNT13 transcript was detected with analysis by quantitative (n = 3) and nested reverse transcription-PCR (n = 4) assays. In contrast, GALNT13 transcripts were detected in 23/23 cytologically involved BM samples obtained at diagnosis of stage 4 NB patients and in 5/27 cytologically noninvolved BM samples obtained from patients with stage 1-4 and 4S and treated stage 4 NB. The quantitative measurements of tyrosine hydroxylase (TH), ganglioside D2 synthase, dopa decarboxylase, and GALNT13 transcript values were compared in the same NB patients, and the results showed that GALNT13 expression was most highly correlated to poor clinical outcome at diagnosis. CONCLUSION: We propose ppGalNAc-T13 as a new informative marker for the molecular diagnosis of BM involvement and the follow-up of minimal residual disease in NB patients.

Adolescent↗

PubMed2004

Nutrient-gene interactions: a single nutrient and hundreds of target genes.

Based on the effects of a selective experimental zinc deficiency in a rodent model we explore the use of transcriptome profiling for assessing nutrient-gene interactions in the liver at the molecular and cellular levels. Zinc deficiency caused pleiotropic alterations in mRNA/protein levels of hundreds of genes. In the context of observed metabolic alterations in hepatic metabolism, possible mechanisms are discussed for how a low zinc status may be sensed and transmitted into changes in various metabolic pathways. However, it also becomes obvious that analysis of such complex nutrient-gene interactions beyond the descriptional level is a real challenge for systems biology.

Animals↗

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↗

PubMed2006

Embryonic stem cell proteomics.

Human embryonic stem cells potentially represent an unlimited source of cells and tissues for regenerative medicine. Understanding signaling events that drive proliferation and specialization of these cells into various differentiated derivatives is of utmost importance for controlling their behavior in vitro. Major progress has been made in unraveling these signaling events with large-scale studies at the transcriptional level, but analysis of protein expression, interaction and modification has been more limited, since it requires different strategies. Recent advances in mass spectrometry-based proteomics indicate that proteome characterization can contribute significantly to our understanding of embryonic stem cell biology. In this article, we review mass spectrometry-based studies of human and mouse embryonic stem cells and their differentiated progeny, as well as studies of conditioned media that have been reported to support self-renewal of the undifferentiated cells in the absence of the more commonly used feeder cells. In addition, we make concise comparisons with related transcriptome profiling reports.

Animals↗

PubMed2006

Identification of common pathways mediating differentiation of bone marrow- and adipose tissue-derived human mesenchymal stem cells into three mesenchymal lineages.

Mesenchymal stem cells derived from human bone marrow (hBMSCs) and human adipose tissue (hAMSCs) represent a useful source of progenitor cells for cell therapy and tissue engineering. However, it is not clear what the similarities and differences between them are. Like hBMSCs, hAMSCs can differentiate into osteogenic, adipogenic, and chondrogenic cells. Whether MSCs derived from different tissue sources represent fundamentally similar or different cell types is not clear. Given the possible different sources of MSCs for cell therapy, a comprehensive comparison of the different MSCs would be very useful. Here, we compared the transcriptome profile of hAMCS and hBMSCs during directed differentiation into bone, cartilage, and fat. Our data revealed considerable similarities between bone marrow-derived MSCs (BMSCs) and adipose tissue-derived MSCs (AMSCs). We uncovered an interesting bifurcation of pathways in both BMSCs and AMSCs, in which osteogenesis and adipogenesis appear to be linked in a differentiation branch separate from chondrogenesis. Our data suggest that although a set of common genes may be needed for early differentiation into all three lineages, a different set of signature genes is associated with maturation into fully differentiated cells. The recruitment of different late differentiation factors explains and supports our conclusion that BMSCs differentiate more efficiently into bone and cartilage, whereas AMSCs differentiate better into adipocytes. This study not only generated a rich database for continuing molecular characterization of various MSCs but also provided a rational basis for assessing qualities of MSCs from different sources for the purpose of cell-based therapy and tissue engineering.

Adipose Tissue↗

PubMed2026

Non-structural maintenance of chromosome condensin I complex subunit H knockdown suppresses malignant progression of esophageal squamous cell carcinoma via the Wnt/β-catenin signaling pathway.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) remains a major cause of cancer-related mortality, and effective therapeutic targets are still limited. Non-structural maintenance of chromosome condensin I complex subunit H (NCAPH) has been implicated in tumorigenesis; however, its clinical relevance, functional roles, and underlying mechanisms in ESCC are not fully defined. We aimed to characterize the expression pattern, prognostic value, biological functions, and mechanistic basis of NCAPH in ESCC. METHODS: Public datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to evaluate NCAPH expression and clinical associations. Single-cell RNA sequencing (scRNA-seq) data were used to map cell-type-specific distribution of NCAPH in tumor and adjacent tissues. NCAPH was silenced in KYSE150 and KYSE510 cells using lentiviral short hairpin RNAs (shRNAs), followed by Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, and Transwell migration/invasion assays. A nude mouse xenograft model was established to assess the effect of NCAPH knockdown in vivo. RNA sequencing (RNA-seq), quantitative polymerase chain reaction (qPCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) were performed to explore potential mechanisms. RESULTS: NCAPH was consistently upregulated in ESCC across multiple cohorts and was associated with unfavorable clinicopathological features and poorer survival. Functional assays demonstrated that NCAPH knockdown significantly inhibited ESCC cell proliferation, migration, invasion, and clonogenic growth. In vivo, NCAPH silencing suppressed xenograft tumor growth. Mechanistically, transcriptomic profiling and molecular validation indicated attenuation of Wnt/β-catenin signaling following NCAPH depletion, accompanied by reduced β-catenin and downstream targets. CONCLUSIONS: NCAPH promotes malignant progression of ESCC, at least in part through activation of the Wnt/β-catenin pathway, and may serve as a potential biomarker and therapeutic target.

Esophageal squamous cell carcinoma (ESCC)↗

PubMed2026

A cuproptosis-related lncRNAs-based risk signature for predicting prognosis and immune status in glioma.

BACKGROUND: Glioma is one of the most prevalent primary malignant brain tumors, characterized by poor prognosis and limited treatment options. Recent studies have identified cuproptosis, a novel copper-dependent form of regulated cell death, as a critical mechanism involved in tumor progression. However, the role of cuproptosis-related long non-coding RNAs (lncRNAs) in glioma remains not fully clarified. This study aimed to develop and validate a prognostic model based on cuproptosis-associated lncRNAs to predict patient outcomes and guide individualizing therapeutic strategies. METHODS: Transcriptomic profiles and clinical data were obtained from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and the Chinese Glioma Genome Atlas (CGGA) databases. Cuproptosis -related prognostic lncRNAs were filtered via univariate and multivariate Cox and Least absolute shrinkage and selection operator (LASSO) regression analyses, which were selected to establish a prognostic model for glioma. Samples were divided into high- and low-risk groups, and the predictive performance of the prognostic model was evaluated based on receiver operating characteristic (ROC) curves, Kaplan-Meier (K-M) survival curves, and a nomogram. In addition, immune cell infiltration, tumor mutational burden (TMB), immunophenoscore (IPS), Tumor Immune Dysfunction and Exclusion (TIDE) and drug sensitivity were analyzed. Expression levels of selected lncRNAs and proteins were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: An 11-lncRNA signature associated with cuproptosis was established, and the risk score derived from this model was identified as an independent prognostic factor for glioma. The model exhibited excellent predictive ability, with area under the curve (AUC) values of 0.880, 0.913, and 0.866 for 1-, 3-, and 5-year survival, respectively. Higher TMB, immune checkpoint expression, and IPS were observed in the high-risk group and no significant difference was observed in TIDE between risk groups. Drug sensitivity analysis identified TPCA-1, KIN001-135, and ispinesib mesylate as potential therapeutic agents. Expression validation in glioma cells further supported the biological relevance of the selected lncRNAs. CONCLUSIONS: This cuproptosis-related lncRNA-based signature demonstrates strong prognostic value and may serve as a promising tool for glioma risk stratification and personalized treatment selection.

Glioma↗

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

Multi-omics analysis to uncover constitutive priming and dynamic metabolic reprogramming conferring white rust resistance in Brassica juncea.

White rust, caused by Albugo candida, is one of the most devastating diseases of Indian mustard (Brassica juncea), causing yield losses of up to 90%. Durable resistance sources within cultivated Brassica germplasm remain limited. In this study, near-isogenic lines (NILs) of B. juncea cv. Varuna harbouring resistance from an East European source (Donskaja-IV, possessing a single CC-NB-LRR protein-coding R gene) was used to investigate the molecular basis of resistance through integrated transcriptomic and metabolomic analyses at 48 and 96 hours post-inoculation (hpi). Transcriptomic profiling revealed that the resistant Varuna_WRR line exhibited significantly higher unique transcript expression (18.76%) compared to the susceptible parent (8.41%) during the progression of infection. Principal component analysis showed clear separation between genotypes based on infection status, time, and genetic background. In the resistant line, upregulated genes were enriched in ethylene-activated signaling, protein phosphorylation, endoplasmic reticulum stress response, pectin biosynthesis, and hypersensitive response at 48 hpi, shifting toward programmed cell death, protein ubiquitination, abscisic acid metabolism, and starch biosynthesis at 96 hpi. Conversely, the susceptible line displayed broad downregulation of primary metabolic processes, indicating metabolic exhaustion. Metabolomic analysis demonstrated that the resistant genotype accumulated higher levels of defense-related amino acids (proline, glutamine, glutamic acid, serine, threonine, glycine), carbohydrates, organic acids, and polyamines, supporting enhanced nitrogen assimilation, energy reserves, membrane stability, and signaling. Together, these findings indicate that constitutive priming and dynamic activation of defense signaling, protein turnover, and osmoprotectant accumulation underpin the enhanced resistance in Varuna_WRR against Albugo candida. This integrated multi-omics approach provides valuable insights for breeding durable white rust resistance in Brassica juncea.

Brassica juncea↗

PubMed2026

Hepatocyte-Specific Deficiency of Endoplasmic Reticulum-Associated Degradation Induces Coordinated Innate-Adaptive Immune Responses.

Hepatic inflammation is a defining feature of Metabolic Dysfunction-Associated Steatohepatitis (MASH), yet the specific contributions of individual immune cell populations and their reciprocal interactions remain incompletely understood. In this study, we combined flow cytometry with single-cell transcriptomic profiling to characterize the hepatic immune landscape in a novel model of spontaneous MASH caused by hepatocyte-specific deficiency of endoplasmic reticulum-associated degradation (ERAD). Hepatic ERAD deficiency led to the expansion of multiple immune cell populations in the liver, including CD8+ T cells, macrophages, monocytes, and dendritic cells, accompanied by extensive functional reprogramming of both innate and adaptive immune compartments. Myeloid cells exhibited enhanced phagocytic activity and increased antigen processing and presentation, whereas CD8+ T cells displayed elevated proliferation capacity, DNA repair activity and cytotoxicity. Notably, two functionally distinct triggering receptor expressed on myeloid cells 2 (TREM2)-expressing macrophage subsets emerged during the progression of ERAD deficiency-induced MASH. Depletion of CD8+ T cells increased monocyte infiltration and aggravated liver injury, suggesting that CD8+ T cells exert a previously unrecognized protective role by restraining monocyte recruitment. Collectively, these findings reveal highly coordinated interactions between innate and adaptive cells during MASH progression and identify CD8+ T cells as potential regulators of monocyte infiltration and hepatic injury.

Animals↗

PubMed2026

Glucose-TOR Signaling Regulates Root Hair Elongation in Arabidopsis via the RHD6-RSL4 Transcriptional Cascade.

Root hairs are tubular protrusions of root epidermal cells that expand the root surface area to facilitate water and nutrient uptake. The target of rapamycin (TOR) kinase has been identified as a positive regulator of root hair elongation, and the RHD6-RSL4 bHLH transcriptional cascade is well established as a core module that governs root hair morphogenesis. However, whether TOR signaling acts upstream of the RHD6-RSL4 pathway and how glucose signals are integrated into this transcriptional regulatory network during root hair development remain incompletely understood. In this study, transcriptome profiling combined with pharmacological and genetic functional assays was performed to elucidate the TOR-mediated transcriptional regulatory pathway of root hair elongation in Arabidopsis. Chemical inhibition of TOR triggered genome-wide transcriptional reprogramming in seedling roots, including disruption of auxin and ethylene signal transduction and pronounced downregulation of hundreds of genes related to root hair development. Glucose-activated TOR signaling modulates the expression of root hair-specific (RHS) genes mainly through the core RHD6-RSL4 transcriptional cascade. The transcription of RSL1-RSL5 was strongly dependent on functional TOR activity, whereas RHD6 transcript abundance was specifically induced by glucose-TOR signaling under carbon-starvation recovery conditions. Genetic overexpression of either RHD6 or RSL4 partially rescued root hair elongation defects caused by TOR suppression, confirming that the RHD6-RSL4 cascade functions as a critical downstream transcriptional module of glucose-TOR signaling. Collectively, this work establishes a transcriptional framework in which glucose-TOR signals modulate root hair elongation via transcriptional activation of the master bHLH regulators RHD6 and RSL4.

RHD6-RSL4 cascade↗

PubMed2026

Genome-Wide Characterization of the Apple HD-Zip IV Gene Family and Functional Validation of MdHDZIV3 Under PEG-Induced Osmotic Stress.

The homeodomain-leucine zipper IV (HD-Zip IV) transcription factor subfamily plays essential roles in epidermal development, cuticle formation, lipid metabolism, and environmental adaptation in plants. Despite its biological importance, the HD-Zip IV family has not been systematically characterized in apple (Malus domestica). Here, we identified 17 apple HD-Zip IV genes and named them MdHDZIV1-MdHDZIV17 based on their locations on the chromosomes. The 17 genes showed a nonuniform distribution on eight chromosomes, while the occurrence of both tandem and segmental duplications indicated that family expansion involved more than one duplication mechanism. All MdHDZIV proteins contained the conserved HD, LZ, START, and SAD domains but lacked the MEKHLA domain, consistent with typical HD-Zip IV structural features. Phylogenetic analysis classified MdHDZIV proteins into five groups together with HD-Zip IV members from Arabidopsis thaliana and rice, indicating evolutionary conservation of this subfamily. Collinearity and Ka/Ks analyses revealed that duplicated MdHDZIV gene pairs were mainly subjected to purifying selection. Promoter scanning revealed diverse cis-regulatory motifs associated with hormonal signaling, environmental stress, light response, and epidermal regulation, including ABRE, ARE, W-box, MYC, G-box, and L1-box motifs. Integration of transcriptomic profiling with qRT-PCR validation revealed pronounced tissue-dependent differences in the expression of MdHDZIV genes in leaf, fruit skin, and branch bark. Under PEG6000-induced osmotic stress and NaCl-induced salt stress, 10 candidate MdHDZIV genes displayed gene-specific and stress type-specific expression patterns, with MdHDZIV3 showing strong induction under PEG6000 treatment. Functional validation in apple calli showed that MdHDZIV3 overexpression enhanced PEG tolerance, increased fresh weight, elevated SOD and POD activities, and reduced MDA accumulation under osmotic stress. These findings provide a genome-wide framework for understanding the apple HD-Zip IV gene family.

abiotic stress↗