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PubMed2026

Systematic Identification and Functional Characterisation of Colletotrichum fructicola Effectors During Camellia oleifera Colonisation.

Camellia oleifera is an important woody oil crop in southern China, but its production is severely threatened by anthracnose caused by Colletotrichum fructicola. C. fructicola deploys secreted effector proteins to establish infection. However, systematic identification and functional characterisation of C. fructicola effector genes upregulated during infection remains largely unexplored. Here, we integrated genome-wide secretome prediction with RNA-seq data from C. oleifera leaves inoculated with C. fructicola to identify candidate effectors induced during infection, followed by functional screening, targeted gene deletion, complementation and pathogenicity assays. Five novel effectors required for C. fructicola full virulence were identified, all of which suppressed Bax-induced cell death in Nicotiana benthamiana. Targeted deletion of the corresponding genes in C. fructicola reduced lesion areas by 47%-78% on C. oleifera leaves and by up to 67% on apple fruits, whereas complementation restored their virulence to wild-type levels. Transcriptomic profiling of infected postharvest C. oleifera fruits identified differentially expressed genes enriched in GO terms related to copper ion response, as well as in KEGG pathways associated with phenylpropanoid biosynthesis, taurine and hypotaurine metabolism, and plant-pathogen interactions. In addition, superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities, as well as malondialdehyde content, were altered in C. oleifera leaves inoculated with the effector-deletion mutants compared with those infected with the wild-type strain, suggesting that these effectors may contribute to the modulation of host oxidative stress responses. Taken together, our findings provide genetic and physiological evidence that these effectors contribute to C. fructicola virulence, offering potential targets for anthracnose control.

Colletotrichum↗

PubMed2026

A Multifaceted Interplay Among Hemophagocytosis, Interleukin-18, and Type I Interferon Distinguishes Still Disease From Other Autoinflammatory Diseases.

OBJECTIVE: The unknown pathophysiology and the lack of specific features for systemic juvenile idiopathic arthritis and adult-onset Still disease (collectively known as Still disease; SD) delay diagnosis and appropriate treatment. The goal of this study was to identify features and mechanisms that distinguish SD from other systemic autoinflammatory diseases (SAID). METHODS: Using the SomaScan assay and RNA sequencing (RNA-Seq), we determined the plasma proteomes and immune cell microRNA (miRNA) and RNA transcriptomes of 372 patients with SAID, respectively. Proteomic findings were validated by enzyme-linked immunosorbent assays. SD (n = 72) and non-SD SAIDs (n = 300) were compared to identify distinguishing features of SD. We performed integrated and unbiased analyses of all data sets using weighted gene correlation network analysis to identify feature modules that characterize SD and stratify patients. RESULTS: Elevated plasma heme oxygenase 1 (HO-1) and interleukin-18 (IL-18) strongly correlate and characterize SD but do not associate with general inflammation. SD was characterized by ferroptosis in plasma, type I interferon (IFN) signaling in monocyte transcriptomes, and elevated natural killer cell miRNA-146a-5p, which is an IL-18 induced miRNA. Finally, we identified feature modules that distinguish SD from other SAIDs and stratified patients with SD into two distinct subgroups not attributable to disease activity or inflammation but hemophagocytosis. CONCLUSION: This unprecedented large omics data set of SAIDs revealed that complex interactions among hemophagocytosis, IL-18, and type I IFN signaling characterize SD. Furthermore, two distinct subgroups in patients with SD were distinguished by the degree of hemophagocytic activity. Finally, the large proteomics and RNA-Seq data sets generated in this study can serve as an invaluable resource for the further investigation of SD and other SAIDs.

Humans↗

PubMed2026

Maize ZmMYB59 inhibits post-germinative shoot and root elongation through ZmGA2ox3/10-mediated gibberellin catabolism.

Gibberellin (GA) promotes seed germination, but sustained or excessive GA signaling after germination can lead to aberrant root and shoot elongation. How GA homeostasis is transcriptionally restrained during post-germinative seedling development remains unclear. Using overexpression and gene-edited maize materials, we demonstrate that ZmMYB59 inhibits root and shoot elongation during post-germinative growth. Integrated RNA-Seq and CUT&Tag analyses identified the GA catabolism genes ZmGA2ox3 and ZmGA2ox10 as candidate direct targets of ZmMYB59. Hormone profiling analysis showed elevated bioactive GA1 and GA4 levels in the scutellum and aleurone layer cells of zmmyb59 mutants. Dual-luciferase assays, electrophoretic mobility shift assays, and ChIP-qPCR further confirmed that ZmMYB59 directly binds AC8 cis-elements in the ZmGA2ox3/10 promoters and activates their transcription. The zmga2ox3/10 double mutant, but neither single mutant, exhibited enhanced root and shoot elongation, accompanied by GA4 accumulation. This phenotype was suppressed by exogenous application of the GA biosynthesis inhibitor uniconazole. Transcriptomic and biochemical analyses further revealed enhanced starch degradation, reduced starch content, and increased soluble sugar accumulation in the double mutant. Taken together, these findings reveal that the ZmMYB59-ZmGA2ox3/10 module restrains GA accumulation and starch mobilization after germination, thereby coordinating reserve utilization with post-germinative root and shoot growth in maize.

Gibberellins↗

PubMed2026

Transcriptomic analysis of eggs, rediae and cercariae reveal stage-specific adaptations in the rumen fluke Calicophoron daubneyi.

Rumen flukes, particularly the trematode Calicophoron daubneyi, are emerging parasites of livestock in Europe, yet transcriptomic insights into their environmental and intermediate host stages remain limited. Here, we present a comprehensive transcriptomic analysis of eggs at three distinct developmental stages (freshly excreted, early developmental and eye-spot stages), as well as rediae and cercariae, of C. daubneyi. High-quality RNA-sequencing (RNA-seq) datasets revealed both shared and stage-specific transcriptional profiles with each developmental stage exhibiting its own distinct expression pattern. Subsequent GO-Term enrichment analyses revealed that fully embryonated eggs in eye-spot-stage especially upregulated genes related to cilia assembly, movement and motility, reflecting preparation for miracidial hatching and host-seeking behavior. Rediae showed enhanced transcription of genes involved in diverse metabolic and biosynthetic processes, supporting rapid asexual proliferation within the snail intermediate host. Cercariae exhibited predominant upregulation of genes associated with signal transduction and energy metabolism, indicating the adaptation to its changing environmental conditions. These findings provide the first transcriptomic insights into the biology of C. daubneyi outside the definitive host, reveal molecular mechanisms underlying development, transmission and adaptation to a changing environment and identify stage-specific genes as potential targets for interventions aimed at disrupting the parasites life cycle and controlling rumen flukes in the future.

Animals↗

PubMed2026

Chronic nitric oxide mediates dual-layer gene regulation through mRNA m6A positional remodeling and parallel transcriptional reprogramming.

Nitric oxide (NO) is a pleiotropic free radical that functions as a master regulator of gene expression, and its sustained production within the tumor microenvironment reshapes the epitranscriptomic state of cancer cells. We previously demonstrated that NO inhibits the m6A mRNA demethylases FTO and ALKBH5 through dinitrosyliron complex formation while leaving the methyltransferase METTL3 intact, a demethylase-specific perturbation that increases global m6A on mRNA. Here, integrating m6A-RIP-seq and RNA-seq from triple-negative breast cancer cells, we show that chronic NO does not produce the uniform hypermethylation anticipated from demethylase inhibition. Instead, it redistributes m6A on mRNA, enriching the 5'UTR and coding sequence while depleting the 3'UTR and departing from the canonical stop-codon and 3'UTR topology. We found that the position of m6A, rather than its intensity or mere presence, shapes the outcome, in part by determining which reader protein is predicted to recognize it. In parallel, NO drives a canonical NF-κB and inflammatory transcriptional program. The transcriptional program is independent of the m6A methylome in both which genes respond and how strongly they respond, ruling out a linear methylome-to-transcriptome cascade; even so, m6A position remains associated with the direction of change among responding transcripts. The 3'UTR is the primary site of m6A loss and shows a suggestive computational link to miRNA-mediated regulation. Sense-antisense coordination reinforces the transcriptional response without bridging the two programs. These findings demonstrate that NO not only increases m6A abundance, but it also rewrites the m6A positional code, establishing spatial reprogramming of the epitranscriptome as a previously unrecognized mode of gene regulation.

RNA Methylation↗

PubMed2026

ScRNA-seq analysis reveals the effects of nitrite stress on the endocrine system of the eyestalk in Litopenaeus vannamei.

Nitrite is a harmful substance generated in Litopenaeus vannamei farming systems, largely originating from the inadequate breakdown of surplus feed and shrimp feces. Its accumulation in the water can affect the growth and physiological functions of shrimp, damage the immune system, and even cause mass mortality, thus becoming a key environmental factor restricting the green development of the industry. Under nitrite stress, the eyestalk, as an important neuroendocrine regulatory center in crustaceans, participates in the stress adaptation of the organism and exerts a protective effect by regulating energy metabolism and immune function. However, the molecular regulatory mechanism of the eyestalk in response to nitrite stress remains unclear. In this study, single-cell RNA sequencing (scRNA-seq) technology was used to analyze the heterogeneity of eyestalk cells in L. vannamei under nitrite stress. A total of 18, 394 high-quality cells were obtained, and six major cell subpopulations, including Neurosecretory cell, Motor neuron, Sensory neuron, Interneuron, Neurogliocyte, and Support cell, were identified. Differential expression analysis identified 839 differentially expressed genes, and different cell types showed distinct specific responses to nitrite stress. Functional enrichment analysis indicated that pathways such as glycolysis, oxidative phosphorylation, ribosome function, and endoplasmic reticulum protein processing were significantly activated, while signal transduction and DNA repair-related pathways were inhibited. Further analysis revealed that nitrite stress could induce mitochondrial function changes and trigger oxidative stress, thereby affecting the neuroendocrine system function of the eyestalk. This study provided insights into transcriptomic responses of the eyestalk to nitrite stress at the single-cell level, laying a theoretical foundation for the management of aquaculture environments.

Animals↗

PubMed2026

An XRE-type regulator in Streptococcus mutans plays an important role in brpA expression and oxidative stress tolerance response.

This study used a functional genomics approach to explore the role of a xenobiotic response element (XRE)-type regulator (SMU.405c) in Streptococcus mutans physiology, including the expression of biofilm regulatory protein BrpA. Results showed that deletional mutation of xre significantly reduced the ability of the deficient mutant to grow in the presence of methyl viologen, a commonly used oxidative stressor (P < 0.001). When challenged in a hydrogen peroxide killing assay, the survival rate of the ∆xre mutant was >2-log less than the parent strain after 60 min (P < 0.001). Luciferase reporter fusion assays showed that xre deficiency had no significant effect on luciferase expression when it was under the control of the intact brpA promoter, but the reporter activity increased by >6-fold (P < 0.001) when the reporter gene was fused to a brpA promoter derivative with deletion of a putative XRE-binding box. Electrophoretic mobility shift assay (EMSA) showed that recombinant XRE interacted with the brpA promoter, resulting in an electrophoretic shift of the promoter probes. In vitro transcription assay also showed that inclusion of XRE caused transcription to fall off, significantly reducing full-length brpA transcripts. RNA-seq analysis revealed that deficiency of XRE led to altered expression of >102 genes by >2-fold (P < 0.05), including 28 with increased expression, and 74 with decreased expression. Among the down-regulated were genes for DNA repair and oxidative stress tolerance response. These results suggest that XRE (SMU.405c) in S. mutans plays an important role in brpA expression and oxidative stress tolerance response.IMPORTANCEStreptococcus mutans, a keystone pathogen in human dental caries, primarily lives in the highly diverse microbiota on tooth surfaces, where the conditions are often harsh and fluctuate frequently. Locus SMU.405c was annotated to encode a xenobiotic response element (XRE)-like transcriptional regulator, but no information is available concerning the role of this protein in S. mutans pathophysiology. This study used a functional genomics approach along with molecular and transcriptomic analysis to characterize a deletional xre mutant, and the results showed that xre deficiency in S. mutans resulted in weakened oxidative stress tolerance response and alterations in transcription of >102 genes, including those known to play an important role in cell envelope biogenesis and stress tolerance response. Reporter fusion assay, electrophoretic mobility shift assay (EMSA), and in vitro transcription further demonstrated that the XRE-like regulator encoded by SMU.405c is a repressor of brpA expression and plays an important role in oxidative stress tolerance response.

Streptococcus mutans↗

PubMed2026

CD36 Influences Leukemia Progression in MLL-AF9-Driven AML by Modulating the Leukemia Immune Microenvironment.

CD36, a fatty-acid translocase, is increasingly implicated in acute myeloid leukemia biology and treatment resistance, yet its contribution to leukemogenesis is still unclear. Using the MLL-AF9 model, we transduced hematopoietic stem/progenitor cells (HSPCs) from Cd36-knockout (KO) or wild-type (WT) mice and assessed leukemic potential with in vitro assays, transplants, and transcriptomic, metabolomic, and immune profiling. Both Cd36KO- and Cd36WT-HSPCs underwent efficient MA9-driven transformation, with comparable colony formation and Hox/Meis1 pathway activation, indicating Cd36 is dispensable for leukemic initiation. However, Cd36 deletion markedly attenuated disease progression, reducing leukemic burden and extending survival in irradiated mice (median 22 vs. 15 days, P = 0.001). Effects were strikingly amplified in immunocompetent, non-irradiated recipients (median 63 vs. 22 days, P = 0.002), revealing immune-dependent suppression. Immune profiling showed enhanced CD4⁺ and CD8⁺ T cell infiltration, reduced CD4⁺CD25⁺ regulatory-like cells, and lower Tim-3 expression in Cd36KO-MA9 spleens, consistent with a less exhausted, more effective anti-leukemic T cell response. Despite enhanced T cell infiltration, TCR repertoires remained conserved, indicating functional reprogramming rather than clonal selection. Consistent with a suppressive leukemia immune microenvironment, RNA-seq gene set enrichment analysis identified upregulation of inflammatory (TNFα/NF-κB) and hypoxic pathways in Cd36WT-MA9 cells. Untargeted metabolomics revealed metabolic shifts in Cd36KO cells, involving a reduction in three key metabolites, UDP-GlcNAc, UDP-Galactose/UDP-Glucose, and O-Phospho-L-Serine, that likely support an immune evasion mechanism. These findings demonstrate that while Cd36 is not essential for MLL-AF9-mediated transformation, its cell-intrinsic expression in leukemic cells suppresses anti-leukemic immunity and accelerates progression. This positions CD36 as a promising target to enhance immune surveillance and limit AML aggressiveness.

Acute Myeloid Leukemia (AML)↗

PubMed2026

Transcriptional and phytohormonal regulation of positional ear development reveals yield strategies in maize.

Maize (Zea mays L.) is a vital global crop, contributing ∼37% of annual grain production. Enhancing yield per unit area is crucial for food security, yet research has primarily focused on single-ear traits, overlooking the regulation of double ears-a key determinant of prolificacy. While secondary ears drive yield variability under prolificacy-favoring conditions, the mechanisms governing ear formation across shoot positions remain poorly understood. Here, we performed high-resolution transcriptomic analysis of 66 samples from three ear types (primary, secondary and third) in maize inbred B73. We uncovered distinct hormonal developmental dynamics: strigolactone (SL) signaling genes, particularly SBP transcription factors, dominated in primary (I) ears, whereas ethylene-related genes (e.g., ZmEREB131, ZmACCO35) were enriched in third (III) ears. Functional validation confirmed that knockout of ZmEREB131 and ZmACCO35 accelerated development and elongated ears compared to wild-type, implicating ethylene (ETH) signaling in ear maturation arrest. Notably, SL inhibitor application synchronized primary and secondary ear development, boosting total yield by >20% without compromising primary ear performance. Our study elucidates the transcriptional networks underlying differential ear development and provides actionable strategies for yield improvement through targeted hormonal modulation. These findings advance the understanding of maize inflorescence biology and offer molecular tools for breeding high-yielding varieties.

RNA-seq↗

PubMed2026

Influenza A virus co-infection alters Streptococcus pneumoniae gene expression during upper respiratory tract colonization.

Streptococcus pneumoniae (Spn) asymptomatically colonizes the upper respiratory tract (URT), a niche from which it can transmit to another host or cause invasive disease in the same host. The in vivo transcriptional adaptations that Spn undergoes during nasopharyngeal colonization, particularly during influenza A virus (IAV) co-infection, are poorly understood. Here, we leveraged an established infant mouse model of colonization, shedding, and transmission to perform genome-wide transcriptomic profiling of Spn during mono- and during IAV co-infection. Compared with broth-grown controls, pneumococci isolated from the URT exhibited distinct transcriptional programs, with over 200 genes differentially expressed across time points. Genes involved in carbohydrate uptake and metabolism, glycan degradation, amino sugar and nucleotide sugar metabolism, and amino acid biosynthesis were consistently enriched during colonization, highlighting metabolic adaptation to the nasopharyngeal niche. In contrast, IAV co-infection induced a markedly distinct transcriptional signature, including upregulation of branched-chain amino acid biosynthesis, bacteriocin production, and phosphate acquisition systems. Notably, the pilus islet-1 locus was upregulated during Spn-IAV co-infection. Functional studies demonstrated that while the pilus was dispensable for colonization under mono- and co-infection conditions, it promoted high-shedding events and enhanced inflammatory responses during IAV co-infection. However, reduced inflammation and reduced high-shedding events from pups inoculated with a pilus-deficient mutant did not alter transmission frequency in the infant mouse model. Collectively, our findings define the in vivo transcriptional landscape of Spn during URT colonization and reveal distinct bacterial adaptations during viral co-infection, providing insight into mechanisms that influence pneumococcal persistence, inflammation, and transmission.

RNA-seq↗

PubMed2026

Isoform-Level Analysis Reveals Reproducible Early Changes in Transcript Usage During Human Vaccine Responses.

Vaccine-induced transcriptional responses have been extensively characterized at the gene level, but whether vaccination also alters transcript isoform usage remains largely unexplored. Here, we reanalyzed longitudinal whole-blood RNA-seq data from a discovery cohort of mRNA COVID-19 vaccine recipients using the IsoformSwitchAnalyzeR framework and validated the findings in an independent cohort. Key findings were validated by full-length RNA long-read sequencing and extended to four additional vaccine cohorts covering distinct platforms and pathogens. mRNA vaccination induced a rapid and transient wave of differential transcript usage, peaking at 24 h post-vaccination with 131 isoforms significantly altered across 107 genes, before largely resolving by Day 14. Isoform switching events were reproducible across independent cohorts and confirmed by full-length RNA long-read sequencing. Structural annotation of switching transcripts, including RMI2, WARS1, and NT5C3A, revealed changes affecting predicted protein domains and signal peptides. Notably, highly concordant isoform switching patterns were observed across MVA-based SARS-CoV-2, influenza, and Ebola vaccine cohorts and showed dose-dependent modulation. Overall, differential transcript isoform usage is a rapid and transient feature of the early human immune response to vaccination that was observed across multiple vaccine platforms. These findings reveal an underappreciated layer of transcriptional regulation that complements conventional gene-level analyses and warrants integration into future vaccine immunogenicity studies.

Humans↗

PubMed2026

Mineral-driven molecular signatures of energy metabolism underpin sperm motility in buffalo.

The success of spermatogenesis depends on the interplay of various biomolecules that ultimately determine sperm quality. In this study, RNA-seq analysis of frozen-thawed buffalo sperm (n = 8) revealed the presence of 263 mineral-associated genes (>1 FPKM) in high (n = 4) and 181 in low motile (n = 4) sperm groups. Among these, 177 mineral-associated genes were commonly expressed between them, and the majority were upregulated (>1 fold), LOC102391588 (ncRNA; 37-fold), ZNF699 (26.5-fold), MYZAP (13-fold), etc., in the high motile group. The expression of selected mineral-associated genes was validated. The top enriched functions in commonly expressed genes were regulation of transcription by RNA polymerase II (FDR: 4.7 × 10⁻2; ZNF331, ZNF692, ZNF180, etc.), followed by spermatogenesis (FDR: 2.9 × 10⁻2; CALR3, ADAM18, ADAM29, etc.), proton transmembrane transport (FDR: 4.0 × 10⁻2; ATP6V0E1, ATP1A4, ATP6V1B2, etc.) and flagellated sperm motility (FDR: 2.3 × 10⁻1; CATSPERD, EFCAB6, CABS1, etc.). Additionally, the chromatin remodeling pathway (FDR: 3 × 10⁻2; PTP4A1, PPM1A, DUSP1, etc.) emerged as the most significant and may suggest that these minerals influence genome packaging and sperm functionality. Mineral-associated genes were predominantly associated with zinc (49%), followed by calcium (20%), phosphorus (10%), iron (5%), sodium (2%), potassium (2%), copper (1%) and other trace elements (11%). Although the current study uses frozen-thawed sperm, the findings indicate that mineral-associated genes are crucial for promoting membrane stability, energy production, motility and chromatin integrity, which may contribute to the superior fertilizing ability of sperm.

Animals↗

PubMed2026

Pervasive noise in human pre-mRNA splice site selection.

RNA splicing has historically been thought to be highly efficient and accurate, with little opportunity for deviation from regulated alternative splicing. This dogma has been challenged by recent observations that biological noise may contribute substantially to transcriptome diversity. However, quantitative understanding of stochastic splicing variation is challenging because these transcripts are likely subject to rapid degradation. Here, we use deep sequencing across RNA compartments to track splicing intermediates in human cells and see abundant cryptic splicing associated with genomic features that promote splicing noise. We observe pervasive usage of low-fidelity splice sites, likely due to stochasticity in recruitment or binding of the spliceosome. These sites are turned over quickly and show evidence for nuclear and cytoplasmic degradation, suggesting widespread surveillance and rapid quality control of non-productive transcripts. Our findings provide insights into the propensity for error in RNA processing mechanisms and regulation of alternative splice sites across a gene.

Humans↗

PubMed2026

Firemaster 550 differentially alters gene expression underlying synaptic function in amygdala of prairie voles after gestational or lactational exposure.

Neurodevelopmental disorders often share similar behavioral diagnostic criteria including socioemotional and cognitive deficits. The prairie vole is a uniquely suitable model to study these deficits because they demonstrate strong social affiliation, bi-parental care, and partner attachment. Previously, we have shown that developmental exposure to the flame-retardant mixture Firemaster 550 (FM 550) impairs socioemotional behavior in the prairie vole and alters underlying neuroanatomy and function. However, the mechanisms for impaired pair bonding in males and increased anxiety in females remain unknown, along with the specific critical window(s) of vulnerability. Herein, we exposed prairie vole dams to FM 550 during gestation or lactation, and performed bulk RNA-seq on the amygdala, a hub of socioemotional processing, in their adult offspring. Two mathematically orthogonal methods were utilized for analysis, a linear statistical method and an ensemble machine learning method, incorporating sex as a biological variable. Gene ontology (GO) pathway analysis was performed following both and results compared to identify potential mechanisms of toxicity. GO results indicated consistent expression changes in the Synapse cellular component in all conditions, and implicated glutamatergic signaling specifically. Additionally, gestational exposure (GE) altered genes underlying modulation of synaptic transmission and neural development, while lactational exposure (LE) impacted genes underlying synaptic plasticity, axon guidance, and mitophagy. Machine learning identified disruption of endocrine system development, regulation of biosynthetic processes in GE animals, and suppression of various neuroinflammatory genes across multiple groups. Finally, we performed RNA expression analysis using Nanostring and demonstrated stronger correlation with the differentially expressed genes (DEG) of interest in females than males. Overall, this study demonstrates both the intersecting and distinct impacts of FM 550 exposure on amygdalar gene expression depending on sex and timing of exposure.

Animals↗

PubMed2026

Integrated single-cell and bulk transcriptomic analysis identifies a novel senescent fibroblast subtype associated with poor prognosis in acral melanoma.

BACKGROUND: Acral melanoma (AM) exhibits significant intratumoral heterogeneity, but its tumor microenvironment (TME) and immune regulation remain unclear. This study aims to dissect TME heterogeneity and establish a prognostic model based on key cell subpopulations. METHODS: We collected AM single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Unsupervised clustering, CellChat, and Scissor analysis were performed to characterize cellular heterogeneity, cell-cell communication, and prognosis-related cell subpopulations. Kaplan-Meier analysis was used to assess the prognostic value of key genes, which were further validated by multiplex immunohistochemistry (mIHC). RESULTS: In AM, Mel_C2, C7, and C9 with high SEMA6A and KIT expression were strongly linked to poor prognosis. We further identified a senescent fibroblast subpopulation (sCAF_CDKN2A) characterized by high fibroblast senescence signature (FSS) scores. Integrating Scissor analysis of fibroblast subtypes with bulk prognostic data, we identified COL3A1, VCAN, and KIT as prognosis-associated genes upregulated in poor-outcome-related fibroblast subsets. Cell-cell communication analysis revealed that sCAF_CDKN2A engages in an immunosuppressive network, interacting with regulatory T cells (Tregs) via MIF signaling and receiving signals from exhausted CD8+ T cells through PPIA-BSG interactions. Using transcription factor expression patterns from these fibroblast subtypes, we constructed a prognostic model that effectively stratified patients into distinct risk groups with significant differences in overall survival (OS). mIHC confirmed significantly higher protein levels of SEMA6A and COL3A1 in tumor tissues compared to matched normal tissues. CONCLUSIONS: We established a novel prognostic model for AM and identified sCAF_CDKN2A as an immunosuppressive senescent fibroblast subpopulation driving poor prognosis.

Acral melanoma↗

PubMed2026

Single-cell multiomics reveals exosome-mediated reprogramming and clonotypic remodeling of T cells in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive and immunogenic subtype lacking targeted therapies. While tumor-derived exosomes are known to modulate immune function, their direct impact on human T cell plasticity and antigen specificity remains poorly defined. Here, we conducted a comprehensive single-cell multiomic analysis of primary human T cells exposed to exosomes derived from 17 genomically diverse TNBC cell lines and 35 patient samples. Integrating single-cell RNA-seq, V(D)J sequencing, non-coding RNA profiling, bulk and single-cell cytokine analyses, we uncovered conserved and subtype-specific immunomodulatory programs induced by TNBC exosomes. Exosome-treated T cells displayed skewing toward regulatory and dysfunctional phenotypes, including Th17-like, Treg, and PD-1⁺/PD-L1⁺ Tfh cells. Functional profiling revealed suppression of early activation markers and cytokine responses, alongside selective preservation of cytotoxic features in γδ T and NKT subsets. Transcriptomic and miRNA network analyses demonstrated widespread downregulation of immune effector genes (e.g., HBEGF and TNFSF9) mediated by exosome-delivered regulatory miRNAs (has-miR-98-5p). Notably, exosome-stimulated T cells displayed distinct clonotypic expansions, characterized by the emergence of five tumor-specific γδ TCR clonotypes and 30 unique αβ TCR CDR3 sequences that were absent in mock-treated controls, underscoring the role of exosomes in shaping TCR repertoire dynamics.

Humans↗

PubMed2026

The Small Noncoding RNA, RsaC, Is Essential for Staphylococcus aureus Virulence.

BACKGROUND: Bacterial small noncoding RNAs (sRNAs) play critical roles in virulence, stress adaptation, and host-pathogen interactions. Transcriptomic analyses during infection can help reveal pathogen-derived sRNAs required for pathogenesis, providing valuable insights for the development of novel therapeutic strategies. However, the low abundance of pathogen biomass within the host tissues poses a significant challenge for such analyses. METHODS: We employed 2-step cell disruption to enrich Staphylococcus aureus cells from infected mouse organs and conducted RNA sequencing (RNA-seq) analysis to examine staphylococcal sRNAs expressed during infection. qRT-PCR was used to confirm the gene expression. A knockout mutant of highly expressed sRNA, RsaC, was generated, and RNA-seq under in vivo as well as in vitro aerobic and anaerobic conditions were compared between the wild-type and ΔrsaC strains. Virulence of S. aureus was assessed using both mouse and silkworm survival assays. RESULTS: We identified RsaC as one of the most highly expressed sRNAs in mouse organs with consistent increment over time postinfection. Through gene disruption and complementation, we demonstrated that RsaC is an independent virulence determinant required for full pathogenicity of S. aureus in a murine infection model. In addition, RsaC influenced gene expression in response to oxygen availability and host-associated stress. Further analysis revealed that mutation of 2 genes downregulated in ΔrsaC in vivo, NWMN_RS03420 (sodium: proton antiporter) and NWMN_RS12015 (hypothetical protein), reduced S. aureus virulence in a silkworm model. CONCLUSIONS: These findings identify RsaC as a novel independent virulence determinant that supports S. aureus adaptation within the host.

Animals↗

PubMed2026

Trichoderma reesei Nsd3 transcription factor: pleiotropic roles in development, stress response, secondary metabolism, and cellulase production.

Trichoderma reesei is known for its ability to secrete high amounts of cellulases, enzymes of fundamental importance in generating products from lignocellulosic biomass. Diverse signaling pathways and transcription factors (TFs) control the cellulolytic repertoire in T. reesei to ensure correct adaptation to the environment. Here, we analyzed RNA-Seq data and identified a new potential regulator of cellulase production in T. reesei: a novel TF named Nsd3, a homolog of NsdC from Aspergilli. Deletion of nsd3 reduced vegetative growth and conidiation on solid medium. Phenotypic characterization of the Δnsd3 strain showed that it is more sensitive to osmotic stress, but more resistant to cell wall and oxidative stresses. Our results showed that Nsd3 is a repressor of cellulase expression by directly regulating key genes in the cellulolytic pathway, an unreported role for this TF in fungi. Loss of nsd3 leads to a faster and more robust induction of cellulolytic genes, and higher cellulase and hemicellulase activities. Transcriptional profiling by RNA-Seq, chromatin accessibility profiling by ATAC-Seq, and protein-DNA interaction assays showed that sugar transporters are important targets of Nsd3 during cellulase expression regulation. Combined with microscopy and gene expression analyses, the ATAC-Seq data also highlighted Nsd3 as a central regulator of cell wall remodeling and organization. Furthermore, the transcriptomics also showed that Nsd3 regulates genes involved in secondary metabolism. These results showed that Nsd3 regulates several physiological processes and provide novel insights into the regulatory system of cellulases in T. reesei that can be used in the design of high-performance strains for biorefinery.IMPORTANCETrichoderma reesei is a key player in the production of hydrolytic enzymes for the degradation of lignocellulose biomass, and transcription factors are important targets for genetic engineering to construct cellulase-hyperproducing strains. Here, we identified the transcription factor Nsd3 and characterized its role as a regulator of cellulase production in T. reesei. We applied two powerful genomics methods (transcriptome sequencing and chromatin accessibility sequencing) to unravel the global role of Nsd3 and its regulatory mechanism. Nsd3 participates in various biological processes in T. reesei, including cell wall remodeling, calcium metabolism, and secondary metabolism, in addition to regulating the expression of sugar transporters. Protein-DNA interaction assays demonstrate that Nsd3 acts through important genes to regulate cellulase expression, including ace4, crt1, stp1, and cel1b. Our study provides mechanistic insights about how Nsd3 regulates diverse physiological processes in T. reesei. This work also applied ATAC-Seq for the first time to study chromatin accessibility in T. reesei.

ATAC-Seq↗