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Results for “single-cell RNA sequencing”

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PubMed2026

Tracking GAD-specific T-cell expansions in Type 1 diabetes by intradermal GAD-Alum challenge.

Identifying and monitoring autoreactive T cells that drive beta cell destruction remains a major obstacle to developing effective immunotherapies for type 1 diabetes (T1D). These cells are extremely rare in peripheral blood and cannot be accessed directly from the pancreas. We used intradermal injection of Glutamic Acid Decarboxylase (GAD)-Alum to recruit GAD-specific T cells to accessible sites in the skin and skin-draining lymph nodes (LNs), sampled by skin suction blisters and ultrasound-guided LN aspiration. Peripheral blood samples obtained before GAD injection were restimulated with GAD in vitro to detect reactive CD4+ T cells. Single-cell RNA sequencing (scRNAseq) followed by re-expression of selected T cell receptors (TCRs) confirmed antigen specificity. Up to 70% of T cells at the skin injection site were clonally-expanded and 4 of 14 (28%) re-expressed TCRs were GAD-reactive. In LNs 1 of 14 (4%) clonally-expanded TCRs was GAD-reactive, representing ~0.08% of all T-cells. GAD-reactive cells across compartments displayed Th1 and Th17-associated transcription signatures. These results demonstrate the intradermal autoantigen challenge and scRNAseq, enable direct identification and molecular profiling of autoreactive T cells in vivo. This minimally invasive approach provides a powerful platform for tracking antigen-specific T cells to monitor disease activity and evaluate immune interventions in T1D.

Autoimmunity↗

PubMed2026

Endothelial cell cycle inhibition enables blood vessel maturation to normalize the tumor vasculature.

Dysfunctional tumor vessels promote disease progression, whereas improved function enhances therapeutic delivery. However, current approaches to normalize tumor vasculature have limited efficacy. In vascular malformations, vessels are similarly dysfunctional, with endothelial cell (EC) hyperproliferation impairing arterial-venous specification. These defects are corrected with palbociclib, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) that has beneficial effects on tumor and immune cells, but the effects on tumor vasculature are not well characterized. In our studies, murine mammary tumor ECs (TECs) exhibited disrupted cell cycle and specification, and CDK4/6i promoted TEC cycle control, enabling improved tumor vascular function. To investigate transcriptomic changes, we performed single-cell RNA sequencing (scRNAseq) of treated and untreated tumors, and healthy tissues. CDK4/6i-mediated TEC cycle arrest promoted arterial-venous specification, cellular junctions, and pericyte association, and suppressed glycolytic and immunosuppressive gene expression. These effects were associated with increased vessel perfusion, decreased tumor hypoxia, and a more favorable immune landscape with immunotherapy. In scRNAseq datasets from patients treated long-term with CDK4/6i, TECs exhibited similar transcriptomic changes associated with arterial-venous specification, pericyte recruitment, and immune signaling. Thus, in contrast to current strategies, CDK4/6i-mediated vascular changes may be maintained with continued treatment, highlighting the relevance of modulating TEC cycle to improve vessel maturation/function.

Angiogenesis↗

PubMed2026

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy↗

PubMed2026

Immature Neutrophil Programs Associate With Burn Mortality and Extend Across Critical Illnesses.

Severe burns provoke a systemic "genomic storm," yet cell states associated with divergent outcomes remain unclear. We profiled blood cells by single-cell RNA-Sequencing (73 014 cells) from adult patients with burn injuries within postburn day 17 (n = 4) and healthy donors (n = 5), integrated data with bulk signatures of burn size, inhalation injury, and mortality, and evaluated clinical associations in the American Burn Association National Burn Repository. Burn was associated with emergency hematopoiesis marked by expansion of hematopoietic stem/progenitor-like cells, immature neutrophils, and plasmablast/plasma cell states, alongside depletion of naïve CD4+/CD8+ T cells and dendritic cells. Larger burns (>20% TBSA) showed enrichment of humoral transcriptional programs, including plasmablast/plasma cell activation and suppression of cytotoxic CD8+ T-cell states. In multivariable models, inhalation injury was a stronger predictor of death (adjusted odds ratio [OR] 1.9) than burn size (adjusted OR 1.1) and shared greater overlap with the most perturbed single cells in non-survivors; 55% of co-perturbed cells were neutrophils, implicating granulocyte dysregulation as a common lethal axis. We identified a neutrophil-specific 5-gene panel (OLFM4, RETN, LCN2, ARG1, and BTNL3) that discriminated survivors vs non-survivors after burns (area under the curve [AUC] > 0.9) and generalized to trauma (n = 158; AUC 0.81) and intensive care unit COVID-19 (n = 103; AUC 0.75), providing information orthogonal to conventional biomarkers and severity scores. Cytomorphology corroborated transcriptomic immaturity, with ~2-fold higher band neutrophils and larger neutrophil size in a fatal case. Computational drug-reversal analysis highlighted galectin-1 inhibition as a candidate modulator of mortality-associated neutrophil programs. Together, our findings suggest that immature neutrophils represent a shared immune feature across severe burns and other forms of critical illness.

Humans↗

PubMed2026

REACTOR: REgulon Activity analysis and Comparison Tool for single-cell transcriptOmics Research.

SUMMARY: We introduce REACTOR, a computational tool designed to detect differential activity of transcriptional regulators and their target genes (regulons) in single-cell RNA-sequencing data. It expands the currently available framework for regulon analysis by introducing a robust statistical test to detect differential regulon activity between conditions, such as disease versus control, with multiple replicates. By contrasting different conditions, REACTOR enables identification of key condition- and cell type-specific regulons. To demonstrate the use of REACTOR, we illustrate its performance in a publicly available COVID-19 dataset. AVAILABILITY: REACTOR R-package together with an implementation vignette are available at https://www.github.com/elolab/REACTOR.

Regulon↗

PubMed2026

Immune-Like Malignant Epithelial Programs Shape Tumor-Immune Interactions and Inform Prognostic Stratification in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is characterized by marked cellular heterogeneity, yet how malignant epithelial states contribute to immune regulation and clinical outcomes remains incompletely defined. We integrated single-cell RNA-sequencing data to map the cellular landscape of LUAD and identify malignant epithelial cells based on inferred copy-number alterations. Epithelial states were further examined through trajectory inference, transcription factor analysis, and cell-cell communication profiling. Single-cell-derived genes were subsequently integrated with TCGA and independent GEO cohorts to construct and validate a machine learning-based prognostic signature. Malignant epithelial cells displayed distinct functional programs, including an immune-like state associated with genomic instability, immune-related transcriptional activity, tumor-immune communication, and patient outcomes. The resulting immune-like malignant epithelial cell signature (IMEC-Sig) consistently stratified survival across multiple cohorts. Low IMEC-Sig scores were accompanied by greater immune infiltration, higher immune checkpoint expression, and increased immunophenoscore, whereas high scores were linked to a comparatively immunosuppressive phenotype. Pan-cancer analyses further identified KRT8 as a gene associated with unfavorable prognosis, and functional experiments showed that KRT8 silencing suppressed proliferation, migration, invasion, and colony formation in LUAD cells. Together, these findings connect malignant epithelial heterogeneity with the immune context and clinical outcomes, support IMEC-Sig as a biologically informed prognostic tool, and nominate KRT8 as a potential therapeutic target in LUAD.

Humans↗

PubMed2026

Identification of molecular subtypes in clear cell renal cell carcinoma based on chromatin regulators and tumor immune microenvironment profiling.

In the histological classification of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) accounts for the highest proportion and is the most common subtype. Despite advances in management, it continues to be associated with considerable incidence and mortality. Although surgery and systemic therapies are available, their efficacy is constrained by pronounced intratumoral heterogeneity and treatment resistance. Identifying robust biomarkers and clarifying the underlying biological mechanisms are therefore essential to improving diagnosis, risk stratification and therapeutic decision-making. In this work, we identified two ccRCC molecular subtypes displaying divergent chromatin regulator (CR) profiles and different clinical prognoses. Using the genes differentially expressed between these subgroups, we constructed a CR-related score (CRS) that effectively stratified patients according to survival. More analysis concluded that the low expression of CR was more linked with the immune-activated tumors, which encompassed the immune pathway enrichment, as well as the elevation of numerous immune cell subtypes. Moreover, elevated CRS was associated with improved immunotherapy responsiveness. Drug-sensitivity analyses nominated several candidate agents, and SMARCD3 knockdown in 786-O cells inhibited proliferation and migration and reduced sensitivity to masitinib. Collectively, these findings support the prognostic and therapeutic relevance of CR-related states in ccRCC and provide a framework for future experimental validation of chromatin-regulated tumor-immune interactions.

Humans↗

PubMed2026

A machine learning-derived and functionally validated circadian rhythm signature predicts clinical outcomes and in silico drug sensitivity in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) displays considerable heterogeneity in clinical outcomes, highlighting the need for reliable prognostic biomarkers. While the aberrant expression of circadian rhythm-related genes has been implicated in cancer pathogenesis, its comprehensive role in CRC progression and predicted therapeutic vulnerabilities remains inadequately characterized. METHODS: Bulk and single-cell RNA-sequencing data were integrated from multiple CRC cohorts. A circadian rhythm signature (CRS) was developed through machine learning algorithms and validated for prognostic value. Comprehensive analyses of tumor microenvironment, genomic alterations, and drug sensitivity were performed. Furthermore, the biological function of the core gene, BHLHE40, was validated in CRC cell lines through CCK-8, EdU, and wound healing assays. RESULTS: Single-cell analysis demonstrated an elevated expression signature of circadian rhythm-related genes in dendritic cells. The optimized CRS, comprising 14 circadian rhythm-related genes, successfully categorized patients into high- and low-risk groups. Patients with a high CRS showed markedly poorer overall survival and computationally inferred immunosuppressive features, including reduced CD8+ T cell infiltration and increased M2 macrophage polarization. Genomic analysis revealed enhanced mutation burden in TP53 and alterations in RTK-RAS/WNT pathways. Notably, in vitro assays confirmed that BHLHE40 is significantly overexpressed in CRC cells. Knockdown of BHLHE40 markedly inhibited tumor cell proliferation and migration. Drug sensitivity profiling identified bexarotene and SMER-3 as potential therapeutic options for high-CRS patients. A nomogram integrating CRS with clinical parameters demonstrated superior predictive accuracy for 1-, 3-, and 5-year survival. CONCLUSIONS: The CRS represents a promising prognostic biomarker that reflects tumor immune status and genomic features, providing valuable insights for personalized treatment strategies in CRC.

Circadian rhythm↗

PubMed2026

Single-cell transcriptome revealed the aberrant keratinocytes activation in antigen presentation in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD), a common chronic inflammatory skin disease, has been extensively studied using single-cell genomics. However, keratinocytes, as key effector cells in AD, have underlying mechanisms remain incompletely understood and require further investigation. METHODS: We integrated single-cell transcriptomic data from skin tissues of healthy controls, chronic active AD patients, spontaneously healed AD (SHAD) patients, and an ovalbumin-induced AD mouse model. The study particularly emphasized the gene expression and cellular dynamics of keratinocytes across the different groups, as well as their interactions with immune cells. RESULTS: Compared to healthy controls, we observed significant changes in the keratinocyte transcriptome, cellular state, and keratinocyte-immune cell ligand-receptor interactions in AD skin, particularly the marked activation of genes involved in antigen processing and presentation. Interestingly, such gene activation was not observed in keratinocytes from the ovalbumin-induced AD mouse model, despite its phenotype closely resembling human AD. Furthermore, in SHAD, we identified a recovery of both the ligand-receptor interaction patterns and antigen processing and presentation genes, accompanied by a notable shift in the transcriptome. This involved a significant downregulation of genes related to cytoplasmic transcription and oxidative phosphorylation. Notably, this pattern was not observed in the self-healing mouse model following the removal of ovalbumin stimulation. CONCLUSION: Our results suggest that the persistent activation of antigen processing and presentation pathways in keratinocytes may be a key driver of chronic inflammation in AD. Therefore, redirecting anti-allergic therapeutic strategies from solely targeting immune cells to targeting of keratinocyte-mediated antigen presentation may offer a more effective approach. Furthermore, we raise concerns about the use of ovalbumin-induced mouse models to recapitulate human chronic AD, as the underlying mechanisms may differ significantly.

Dermatitis, Atopic↗

PubMed2026

A contextual activity score (CAS) for inferring ADAR-associated transcriptional activity across RNA-seq, single-cell, and spatial transcriptomics.

BACKGROUND AND OBJECTIVE: Adenosine-to-inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), is a widespread modification involved in neural function, immune regulation, and cancer. The Alu Editing Index (AEI) is the standard metric to estimate ADAR activity but requires raw sequencing reads and is poorly suited for single-cell and spatial transcriptomic data. This study aimed to develop an alternative framework for inferring ADAR-associated transcriptional activity from gene expression data across diverse transcriptomic technologies. METHODS: We developed the Contextual Activity Score (CAS), a framework based on transcriptional signatures from ADAR perturbation experiments. Context-specific signatures were generated for human neurons, mouse neurons, and cancer models to infer ADAR1 and ADAR2 activity. CAS was computed from normalized gene expression matrices using regulon-based enrichment analysis. Performance was evaluated by comparing with the Alu Editing Index across bulk RNA sequencing datasets, simulated sequencing depths, and library preparation protocols. RESULTS: CAS showed strong concordance with the Alu Editing Index across multiple datasets, while remaining robust to reduced sequencing depth and different library protocols. Unlike the Alu Editing Index, CAS can be applied to single-cell and spatial transcriptomic data and enables the independent assessment of ADAR2 activity. In cancer and neuronal contexts, CAS captured biologically meaningful variations in ADAR-associated transcriptional activity at sample, cell-type, and spatial levels. CONCLUSION: CAS provides a scalable approach applicable across multiple RNA-seq protocols for estimating ADAR-associated transcriptional activity using gene expression data. This method, implemented in an open-source R package for broad adoption, expands the ability to study ADAR-associated transcriptional activity across transcriptomic modalities where direct editing quantification is challenging, such as single-cell and spatial transcriptomics.

Adenosine Deaminase↗

PubMed2026

Human Monocytic Models Reveal Genotype-Dependent Inflammatory Programs in VEXAS Syndrome.

OBJECTIVES: VEXAS syndrome is a severe X-linked autoinflammatory disorder caused by somatic mutations in ubiquitin-like modifier activating enzyme 1 (UBA1), with clinical outcomes that vary by UBA1 genotype. We aimed to elucidate genotype-specific inflammatory programs and identify potential therapeutic targets. METHODS: We conducted longitudinal deep phenotyping, including whole-blood RNA sequencing (RNA-seq) and clinical activity assessment. Peripheral blood samples were analyzed by single-cell RNA-seq. Human monocytic cell lines harboring each major UBA1 mutation (p.Met41Val, p.Met41Thr, or p.Met41Leu) were generated and subjected to transcriptomic and functional analyses. RESULTS: Thirteen patients with VEXAS syndrome contributed a total of 79 RNA-seq samples. Among genes upregulated in VEXAS syndrome, RNASE1 showed the strongest correlation with longitudinal disease activity (r = 0.70, FDR < 0.05) and was upregulated in patients' monocytes. In UBA1-mutant monocytic cell lines, genotype-dependent ubiquitination defects were observed in a graded manner (p.Met41Val > p.Met41Thr > p.Met41Leu), even in the absence of exogenous stimuli. These defects were accompanied by unfolded protein response activation, increased pro-inflammatory cytokine production, progressive cell death, and RNASE1 upregulation, all following the same graded pattern, recapitulating patient genotype-phenotype associations. Transcriptomic analyses demonstrated enrichment of pro-inflammatory, interferon, and necroptosis signatures in more severe genotypes. Notably, inhibition of receptor-interacting protein kinase 3 (RIPK3) markedly attenuated all pathological features, including RNASE1 upregulation. CONCLUSIONS: Our UBA1-mutant monocytic cell-line models, representing three distinct genotypes, recapitulate genotype-dependent inflammatory phenotypes that can be modulated by RIPK3 inhibition, providing a translational platform for mechanistic investigation and precision therapy development in VEXAS syndrome.

Journal Article↗

PubMed2026

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans↗

PubMed2026

Receptor-defined targeting of a genomically unique melanoma-enriched noncanonical antigen.

Effective T cell-based immunotherapies require functional receptors that can be engineered and redeployed to recognize tumor-restricted antigens. Noncanonical peptides arising from transcription outside annotated protein-coding regions expand the antigenic landscape of cancer; however, systematic strategies to biologically prioritize and functionally validate such targets remain underdeveloped. Here, we integrated de novo transcript analysis, exon-resolved quantification, RNA in situ hybridization, and immunopeptidomics to identify melanoma-associated noncanonical transcripts and advance candidates through receptor-level validation. Among three recurrent melanoma-associated transcripts, EVA003 emerged as a lead target based on its distinct repeat-enriched genomic architecture, consistent tumor-enriched exon-level expression across independent datasets, and a genomically unique immunogenic core sequence. We demonstrate endogenous presentation of EVA003-derived peptides on HLA-A*03:01 and detect specific reactivity in patient-derived tumor-infiltrating lymphocytes. Single-cell transcriptomic profiling identified a dominant peptide-reactive clonotype, enabling isolation of a naturally occurring T cell receptor. Transfer of this receptor into healthy donor T cells conferred antigen-dependent activation and cytotoxicity against both peptide-pulsed targets and melanoma cells expressing EVA003 endogenously. Together, these findings establish a biologically informed strategy for prioritizing noncanonical tumor antigens and demonstrate that genomically unique, tumor-enriched noncanonical peptides can be presented to molecularly defined receptors capable of mediating cancer cell killing. These findings support the integration of prioritized noncanonical antigens into engineered T cell therapeutic strategies.

Humans↗

PubMed2026

From wild to domestic: Single-cell transcriptomic perspectives on hippocampal regulation and evolution.

How domestication shapes brain evolution remains an open question. In this study, we integrated single-nucleus RNA sequencing (snRNA-seq), population genomics, and machine learning to investigate the hippocampal evolution under domestication. Across-species comparisons revealed that hippocampal cell type profiles are largely conserved across vertebrate species, while supporting the presence of adult hippocampal neurogenesis in birds. We further found that domestication and selective breeding likely influence the cellular composition and molecular regulation of the hippocampus. Our findings provide cellular evidence supporting the hypothesis that domestication affects adult hippocampal neurogenesis. Additionally, we showed that genes associated with neural progenitor cells (NPC) states and cell-marker programs are enriched for signatures of selection. Many of these genes function as regulators of neurogenesis and pathways mediating stress and fear reduction. Specifically, we identified selection at the FKBP5 promoter that may influence its expression in the NPC lineage, potentially contributing to stress-response regulation during domestication. Collectively, these results suggest that domestication is associated with hippocampal remodeling as part of an adaptive response to human-managed environments. This study provides a cellular and genetic perspective on how domestication reshapes the brain and offers a basis for further investigation into the mechanisms of neural evolution within the context of microevolution.

Animals↗

PubMed2026

Integrated Genomic and Proteomic Analysis Reveals T-B Lymphocyte Signatures in the MYCN Driven "Immune Desert" of Specific Neuroblastoma Subtypes.

AIMS: This study aims to systematically dissect how MYCN amplification shapes the immunosuppressive tumor microenvironment (TME) in high-risk neuroblastoma, elucidating key mechanisms underlying immune evasion. METHODS: We performed an integrated multi-omics analysis of bulk RNA-seq (n = 721), single-cell RNA-seq (n = 9), proteomic data (n = 49) and spatial transcriptomics (Visium, with external validation in melanoma). Analyses included unsupervised clustering, cell-cell communication inference, transcriptional regulatory network reconstruction, and spatial proximity assessment to map the immune landscape. RESULTS: A distinct molecular subtype (Class C), defined by MYCN amplification and poor prognosis, exhibited a comprehensive "immune desert" phenotype characterized by low immune scores and minimal leukocyte infiltration. Single-cell analysis confirmed significant depletion of T and B lymphocytes within the Class C TME. Dysregulated transcriptional networks were identified, including upregulation of REL and EOMES in T cells-with EOMES potentially driving exhaustion via regulation of Transient Receptor Potential (TRP) genes, and REL inhibition enhancing cytotoxic function in vitro. A unique immunosuppressive B-cell subset (B7) engaged in enhanced crosstalk with exhausted T cells and harbored a MYC-centered network linked to cell cycle dysregulation and poor survival. Spatial transcriptomics revealed significant proximity between B7-active regions and Treg/exhaustion-enriched areas, externally validated in melanoma. Proteomic data validated elevated REL expression in MYCN-amplified tumors. CONCLUSION: This work delineates the immunosuppressive architecture of MYCN-driven neuroblastoma, revealing novel regulatory nodes within specific lymphocyte compartments. Integrating single-cell, spatial, and proteomic evidence, we propose REL inhibition as a therapeutic candidate, the EOMES/TRP axis as a bioinformatically supported hypothesis, and the B7/MYC hub as a hypothesis supported by transcriptomic and spatial evidence.

Humans↗

PubMed2026

Integrative quantum and systems biology of cancer: From molecular fluctuations to ecological outcomes.

This review treats cancer as a multiscale adaptive system, asks what the framework must predict to be worth adopting, and separates at each scale what the evidence establishes from what is proposed. It is an expert narrative synthesis, not a systematic review, and states the limits of that design. Proton transfer and tautomeric shifts contribute to spontaneous mispairing but do not license claims of directed or non-random mutation: replication timing, three-dimensional chromatin organization, sequence context and known mutagenic processes explain most mutational heterogeneity, leaving any quantum contribution as a residual against that baseline. The Waddington quasi-potential is bounded: outside detailed balance the dynamics are not gradient-derivable and require a probability-flux term. Hysteresis, rate-limited bimodality and return to state after perturbation distinguish an attractor from a transcriptomic cluster. Single-cell karyotype and live-imaging evidence supports whole-genome doubling as an unstable intermediate of heterogeneous origin and context-dependent consequence, not a uniform adaptive strategy. Systems and synthetic biology, virtual cells and digital twins are assessed against benchmarks, not promise. Tissue-scale ecology is reported with the spatial measurements now quantifying it, including evidence that stromal niche construction is not uniformly tumor-supporting. RNA modification is a layer in its own right, showing that the interpretation of a regulatory signal, not its magnitude, is biologically decisive. A dedicated section states the framework's commitments, the observable and evidence at each scale, and what would falsify them, asking what this adds to somatic mutation theory with clonal evolution and plasticity.

Neoplasms↗

PubMed2026

Decoding the landscape of cell-type-specific co-expressed transcription factors in soybean.

Soybean (Glycine max) is an essential source of protein and oil with high nutritional value for human and animal consumption. To enhance our understanding of soybean biology, it is essential to have accurate information regarding the expression of each of its protein-coding genes. Here, we present Tabula Glycine max, a soybean single-cell resolution transcriptome atlas. This atlas comprises single-nucleus RNA-sequencing data from ten different G. max organs and morphological structures constituting the entire soybean plant. These nuclei are grouped into 156 different clusters based on their transcriptomic profiles. The breadth of various organs, tissues and cell types represented in Tabula Glycine max reveals that the pattern of co-expressed transcription factor genes is sufficient to define most cell types based on their function and organ of origin. Defining cell-type-specific co-expressed transcription factor genes offers a new perspective to engineer cell-type-specific programmes and enhance the biology of unique soybean cell types. This cellular resolution and breadth make the Tabula Glycine max an exceptional resource for the plant and soybean communities.

Journal Article↗

PubMed2026

Amino acid reprogramming and biofilm-specific tricarboxylate transporters in PET-degrading Piscinibacter sakaiensis.

Plastic-degrading bacteria predominantly colonize polymer surfaces as biofilms, yet it remains unclear whether the biofilm phenotype contributes to metabolism beyond retaining extracellular enzymes. Here, we combine population-level RNA-sequencing across three conditions-biofilm cells on polyethylene terephthalate (PET), planktonic cells incubated with PET, and planktonic cells on maltose-with single-cell Raman spectroscopy to characterize the PET response of Piscinibacter sakaiensis (formerly Ideonella sakaiensis). This integrated approach reveals two metabolically distinct response layers. A carbon-source-driven response shared by all PET-exposed cells is dominated by a broad amino acid reprogramming, led by upregulation of branched-chain amino acid transport genes, enhanced serine biosynthesis, and reduced chemotaxis. A biofilm-specific layer selectively induces tripartite tricarboxylate transporter genes from three distinct genomic loci. This transcriptional feature is accompanied by a single-cell phenotype consistent with a protein-rich and saturated membrane. These results suggest that biofilm formation is not limited to enzyme retention but is associated with selective activation of transport systems, consistent with a putative role in capturing PET-derived intermediates at the polymer interface. This two-layer model separates general metabolic adaptation to PET from biofilm-specific functions and provides a framework for understanding how surface-associated bacterial physiology contributes to plastic degradation.IMPORTANCEPolyethylene terephthalate (PET) degradation in natural and engineered environments is largely mediated by surface-attached microbial communities, yet the physiological role of biofilm state during plastic degradation remains poorly understood. Using the model PET degrader Piscinibacter sakaiensis, we show that biofilm-associated cells are not simply retained near the polymer surface but exhibit a distinct metabolic program characterized by selective induction of tripartite tricarboxylate transporters. In contrast, extensive amino acid reprogramming occurs in both biofilm and planktonic PET-exposed cells, indicating that it is driven by carbon source rather than surface attachment. These findings reveal that PET degradation involves two separable physiological layers: a general metabolic response to PET-derived carbon shared across cell phenotypes, and a biofilm-specific transport response potentially linked to substrate capture at the plastic interface. This work advances our understanding of how microbial physiology is organized during plastic biodegradation and identifies transport processes as previously unrecognized components of PET-degrading biofilms.

PET biodegradation↗