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PubMed2026

Volumetric DNA microscopy for mapping spatial transcriptomes in three dimensions.

The architecture and function of biological systems are inherently three-dimensional, yet most existing spatial transcriptomic technologies remain restricted to thin tissue sections, limiting their capacity to resolve cellular organization and microenvironments within intact tissue volumes. To address this limitation, we developed volumetric DNA microscopy, a scalable, optics-free approach for spatial transcriptome profiling directly within intact biological specimens. The method encodes spatial information into DNA molecules that form a dense intermolecular network in situ, enabling the reconstruction of three-dimensional spatial relationships through short-read sequencing and computational analysis. Here we detail the complete workflow including in situ cDNA synthesis, spatial encoding through DNA nanoball formation, dual-scale proximity bridging between neighboring nanoballs and spatial reconstruction via geodesic spectral embedding. Sequencing libraries can be generated within 7-8 d by a competent graduate-level molecular biologist, followed by standardized downstream computational analysis. Because the workflow requires only routine molecular biology reagents and a benchtop sequencer, volumetric DNA microscopy provides a versatile platform for exploring genetic and morphological features in intact tissues.

Spatial Transcriptomics↗

PubMed2026

Transcriptomic analysis reveals the molecular mechanisms underlying the inhibition of Mytilus edulis attachment by biofouling control agents.

This study combined acute toxicity assays, phenotypic quantification, and transcriptomic profiling to systematically investigate the inhibitory effects and molecular regulatory mechanisms of a novel alkylamine-based antifouling agent on survival, byssus secretion, and attachment behavior of juvenile Mytilus edulis. The 96 h-LC50 of the agent to juvenile M. edulis was 8.84 mg/L, and 10 mg/L of the agent completely inhibited mussel attachment within 24 h, significantly reducing byssal thread number, length, and diameter while increasing detachment frequency, resulting in irreversible attachment failure. Transcriptomic analysis identified 2746 differentially expressed genes, which were mainly enriched in pathways including signal transduction, immune defense, stress response, cytoskeleton organization, and protein binding. KEGG and GSEA enrichment revealed that the antifouling agent activated the MAPK stress signaling pathway, disturbed transcriptional regulation, and impaired intracellular homeostasis and cytoskeletal stability, thereby synergistically suppressing the expression of key byssal protein genes including mfp-1 and mfp-3 and ultimately blocking byssus synthesis and adhesion. This study clarifies the multi-pathway molecular mechanism underlying antifouling agent-induced attachment inhibition in M. edulis, and provides core molecular targets and theoretical support for developing efficient, specific antifouling activity, and potentially applicable marine antifouling technologies.

Animals↗

PubMed2025

HallmarkGraph: a cancer hallmark informed graph neural network for classifying hierarchical tumor subtypes.

MOTIVATION: Accurate tumor subtype diagnosis is crucial for precision oncology, yet current methodologies face significant challenges. These include balancing model accuracy with interpretability and the high costs of generating multi-omics data in clinical settings. Moreover, there is a lack of validated models capable of classifying hierarchical tumor subtypes across a comprehensive pan-cancer cohort. RESULTS: We present a graph neural network, HallmarkGraph, the first biologically informed model developed to classify hierarchical tumor subtypes in human cancer. Inspired by cancer hallmarks, the model's architecture integrates transcriptome profiles and gene regulatory interactions to perform multi-label classification. We evaluate the model on a comprehensive pan-cancer cohort comprising 11 476 samples from 26 primary cancers with 405 subtypes up to eight levels. The model demonstrates exceptional performance, achieving 5-fold cross-validation accuracy between 85% and 99% for tumor subtypes labeled with increasing details of genomic information. It also shows good generalizability on a validation dataset of 887 samples, assessed using three metrics that consider tumor subtypes at individual, combined, and sample levels. Benchmarking and ablation experiments show that hallmark-based embeddings slightly influence model performance, while the integrated multilayer perceptron plays a significant role in determining classifier accuracy. Additionally, we use the SHAP method to link cancer hallmarks with genes, identifying key features that influence model decisions. Our findings present a biologically informed machine learning framework capable of tracking tumor transcriptomic trajectories and distinguishing inter- and intra-tumor heterogeneity in pan-cancer. This approach holds promise for enhancing cancer diagnostics. AVAILABILITY AND IMPLEMENTATION: HallmarkGraph is accessible at https://github.com/laixn/HallmarkGraph.

Humans↗

PubMed2026

Comprehensive transcriptomic analysis of BjGL1-knockout Brassica juncea: novel insights into leaf trichome formation.

Brassica juncea is a common cruciferous crop, which can be used not only for oil extraction but also as condiments and medicinal materials. It is regarded by both traditional medicine and modern nutrition science as a food with combined dietary and health promoting value. Leaf trichomes are hair-like structures differentiated from epidermal cells and constitute an important barrier against biotic and abiotic stresses, playing a crucial role in enhancing plant resistance and thus possessing significant scientific relevance. In this study, the phenotype and gene editing site of BjA06.GL1 and BjB02.GL1 knockout mustard T1 generation plants were identified. Then, RNA sequencing was performed to compare the leaf transcriptome profiles between gene-edited lines and wild-type plants, with the aim of elucidating the molecular regulatory mechanisms by which BjGL1 controls leaf trichome development and associated biological processes in mustard. The sequencing data showed that, on average, 90.64% of the reads uniquely aligned to the Brassica juncea (Xuecai) reference genome. A total of 4,604 differentially expressed genes were identified in this study. Compared with the gene knockout mutant, 1,831 genes were significantly upregulated and 2,773 genes were downregulated in mustard leaves with trichomes. The differentially expressed genes were mainly enriched in pathways related to cytochrome P450 (CYP), transporters, environmental adaptation, and plant-pathogen interactions. These pathways are closely associated with secondary metabolite biosynthesis, transmembrane transport, and responses to abiotic stress and pathogen defense. qRT-PCR validation confirmed consistent expression trends of trichome regulatory genes screened from transcriptome data. This study provides an important theoretical basis for elucidating molecular mechanisms potentially contributing to trichome formation in mustard.

Mustard Plant↗

PubMed2026

Molecular mechanisms of neuroendocrine regulation of molting in the Chinese mitten crab (Eriocheir sinensis): A transcriptomic analysis based on eyestalk ablation model.

Molting disability severely restricts the sustainable aquaculture of the Chinese mitten crab, yet the neuroendocrine mechanisms coordinating physiological responses remain poorly understood. Using unilateral eyestalk ablation to remove the primary source of molt-inhibiting hormone (MIH), we performed time-resolved transcriptomic profiling of the thoracic ganglion at 24 h (early premolt) and 48 h (ecdysis) post-ablation. We identified 2825 differentially expressed genes and uncovered a biphasic molecular response. At 24 h, the thoracic ganglion activates pathways associated with neuromuscular adaptation, oxidative stress, and cardiac muscle contraction. Notably, the arachidonic acid metabolism pathway is selectively rewired: cytochrome P450 ω-hydroxylases (CYP2J2, CYP4V2) are upregulated, while competing branches (epoxide hydrolase, cyclooxygenase) are suppressed, promoting local synthesis of the potent vasoconstrictor 20-HETE within the thoracic ganglion. This enzymatic switch provides a mechanistic link between MIH withdrawal and the local generation of elevated hemolymph pressure required for molting. By 48 h, the transcriptional program shifts toward chitin-based extracellular matrix remodeling, glycosphingolipid biosynthesis, and synaptic reorganization. Collectively, our findings redefine the thoracic ganglion as an active neuroendocrine integrator that translates reduced MIH signaling into phased physiological outputs, revealing a "neuro-endocrine-hemolymph pressure" regulatory axis. This study provides novel molecular targets (e.g., CYP2J2, CHS1, UGCG) for mitigating molting disability in E. sinensis aquaculture.

Animals↗

PubMed2026

Genome-wide transcriptional landscape of Mycobacterium tuberculosis during acute lung infection.

Tuberculosis (TB) remains a major global health burden, yet the mechanisms by which Mycobacterium tuberculosis (Mtb) adapts to host environments to drive disease pathology are incompletely defined. A key limitation has been reliance on axenic culture systems that fail to recapitulate the complex, host-imposed stresses encountered by Mtb in vivo. Here, we report the first microarray-based genome-wide transcriptomic profiling of Mtb in rabbit lungs with active TB, which closely mirrors human disease features, including granuloma heterogeneity, necrosis, and cavitation. Using Mtb RNA isolated from infected lung homogenates or broth-culture, we capture bacterial transcriptional states shaped by the host microenvironments. The transcriptional data analyses reveal extensive, context-dependent reprogramming of Mtb metabolic, respiratory, and stress-response networks that diverges markedly from in vitro expression profiles, including activation of stress adaptation, lipid catabolism, nucleic acid metabolism, and transcriptional regulation pathways. These data uncover pathways and networks that are selectively engaged in vivo and likely critical for Mtb survival within granulomatous lesions. Our findings demonstrate that transcriptional states most relevant to TB pathogenesis are underrepresented in standard lab-grown Mtb models and highlight the importance of in vivo bacterial profiling. By characterizing Mtb gene expression within diseased lungs, this study provides a systems-level framework for understanding TB pathogenesis and reveals in vivo-essential pathways, offering potential targets for translational drug discovery and the development of more effective anti-TB therapies.

Animals↗

PubMed2026

From immature to mature epithelium: unveiling structural dynamics and transcriptional programs in rainbow trout intestinal barrier.

The intestinal epithelium is crucial for nutrient absorption, immune defense, and barrier function in farmed fish. However, the molecular mechanisms underlying its development and maturation in salmonids remain poorly characterized, hindering our ability to address pervasive gut health challenges in aquaculture. In this study, we use the RTgutGC cell line to implement an epithelial maturation model with the aim of characterizing the global transcriptional program in rainbow trout (Oncorhynchus mykiss). We evaluated in vitro culture conditions to generate a polarized epithelial barrier with high transepithelial electrical resistance (TEER = 75.8 Ω × cm2), low permeability (6.2 × 10-6 cm/s), and well-defined apical specializations, including microvilli-like structures and clusters of these structures (brush border). Comparative transcriptomic profiling between immature (7 days post-seeding, dps) and mature (28 dps) epithelia revealed 3,817 differentially expressed genes (DEGs). Functional enrichment analysis showed that maturation was characterized by the downregulation of proliferative and ribosomal pathways and the concerted upregulation of processes critical for barrier function, including transmembrane transport, proteolysis, cell adhesion, extracellular matrix organization, and tight junction assembly. We identified a core set of 60 genes indicators of epithelial maturation, encompassing solute transporters (slc26a6, slc43a2), tight junction proteins (tjp1, cldn1, cldn3, cldn5, cldn18, among others), and structural components essential for microvilli formation and polarization (cdhr5b, pard6a). By integrating ultrastructural, functional, and transcriptomic data, this study established a framework for future mechanistic investigations into gut development and maturation in vitro. This set of mature epithelium indicators has diverse applications, such as the design of nutritional and pharmacological interventions to improve gut health and resilience in farmed fish.

Animals↗

PubMed2026

OsICL-associated metabolic reprogramming during dehydration in rice is regulated by ABA and modulated by ACC and its metabolites.

Drought coordinates hormonal, transcriptional, and metabolic reprogramming, but how abscisic acid (ABA) and 1-aminocyclopropane-1-carboxylic acid (ACC) jointly shape cereal dehydration responses remains unclear. We integrated hormone profiling, transcriptome and promoter analyses, synthetic promoter assays, and metabolite profiling in rice. ABA and ACC contents increased markedly in rice shoots under moderate soil water deficit. Combined ABA + ACC treatment showed larger absolute overlaps with dehydration-responsive genes than either ABA or ACC treatment alone in shoots; in roots, this pattern was observed for induced but not repressed genes. Promoters of dehydration- and ABA-inducible genes were enriched in ACGT-core motifs, including a CGTACG core preferentially embedded in ACGTACGT, designated the eXtended ACGT box (Xbox). Multimerised Xbox conferred transcriptional induction under soil water deficit and in response to ABA. OsICL was induced under soil water deficit and by ABA or ACC; in shoots, combined ABA + ACC treatment produced the highest mean transcript accumulation. OsICL overexpression and knockout lines showed altered organic-acid, sugar, and amino-acid profiles, particularly under soil water deficit, but several metabolites changed in the same direction in both line classes. These findings support an ABA-centred, ACC-modulated model of dehydration-responsive transcription and associate OsICL regulation with broader, condition-dependent changes in primary metabolism.

Oryza sativa↗

PubMed2026

Intraductal Papillary Squamous Neoplasm (IPSN) of the Pancreas: Histological and Molecular Characterization of a Novel and Distinct Intraductal Cancer Precursor.

We report 6 intraductal papillary squamous neoplasms (IPSNs) of the pancreas, a rare but distinctive tumor whose biological features remain largely unknown. Five cases were investigated using an integrated approach combining histomorphological evaluation, immunohistochemistry, and multiregional molecular profiling through whole-exome DNA sequencing and whole-transcriptome RNA sequencing. Only targeted DNA sequencing was available on a sixth recently diagnosed case. Histologically, the intraductal lesions were characterized by large, confluent papillae with fibrovascular cores lined by multilayered epithelial cells with diffuse squamous differentiation. All cases harbored a concomitant invasive carcinoma. The associated invasive carcinomas consistently included a pancreatic tubular/ductal adenocarcinoma; in 5 cases, a poorly differentiated squamous cell carcinoma was also present, the proportion/features of which met the diagnostic criteria of adenosquamous carcinoma in 2 of them. Genomic analyses revealed that IPSNs and their matched invasive carcinomas shared the majority of somatic alterations, supporting a shared clonal origin for the 2 components. Activating KRAS mutations and biallelic inactivation of CDKN2A were detected in all cases. Recurrent mutations involved members of the SWI/SNF chromatin-remodeling complex and KMT2D. Additionally, FGFR1 and MYC amplifications were identified in 2 distinct cases (1 case each). Molecular alterations restricted to the invasive component involved mediators of the transforming growth factor-β signaling pathway. Transcriptomic profiling demonstrated a basal-like expression pattern in all IPSNs and squamous cell carcinomas, although in 2 cases, the matched pancreatic tubular/ductal adenocarcinoma shifted toward a classical transcriptomic subtype. In conclusion, through integrated histological assessment and multiregional molecular sequencing, we demonstrate that IPSN represents a bona fide precursor of invasive pancreatic cancer, a new addition to the intraductal neoplasms category. This study challenges the current paradigm that pancreatic squamous epithelium plays no role in the initiation of pancreatic carcinogenesis, providing the first evidence of its involvement in early tumorigenic processes and yielding immediate implications for pancreatic tumor classification and biological understanding.

Humans↗

PubMed2026

Comparative transcriptomics reveals hormone signaling and MADS-box genes in divergent development of inflorescences and tendrils in grapevine lateral shoots.

Hormone signaling and MADS-box genes regulate grapevine tendril and inflorescence growth divergence, offering molecular insights for managing tendril growth. Grapevine (Vitis vinifera L.) tendrils and inflorescences are homologous organs; however, their divergent development has important agronomic consequences because excessive tendril growth increases vineyard management costs. To explore the regulatory mechanisms, we compared the inflorescence-prone cultivar 'Einset Seedless' (ENT) with the tendril-prone cultivar 'Pinot Noir' (PN) using anatomical observation, transcriptome analysis of specific tendril nodes, and functional characterization of MADS-box genes. ENT exhibited a higher flowering rate at tendril nodes 1-4 than PN. Transcriptome profiling of specific tendril nodes uncovered 549 differentially expressed genes (DEGs) through an intersection/exclusion strategy, with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicating that hormone and mitogen-activated protein kinase (MAPK) signaling were the primary candidates driving the divergence. To assess the spatiotemporal dynamics of these DEGs, we performed Mfuzz clustering, which revealed that multiple expression trajectories were highly consistent with the flowering gradient across different ENT and PN nodes. Plant hormone signal transduction was the predominantly enriched pathway across all dynamic clusters, highlighting the centrality of phytohormones in this process. Guided by this transcriptional evidence, we measured endogenous zeatin and gibberellin (GA₃) contents in the nodal tissues. Remarkably, the zeatin-to-GA₃ ratio not only paralleled the flowering gradient but also correlated with the cluster expression trajectories, providing physiological evidence for a cytokinin-gibberellin interaction model governing organ divergence. Additionally, we analyzed the differentially expressed transcription factors among the DEGs and identified a MADS-box gene, FRUITFULL-LIKE (VvFUL-L), which was markedly upregulated in PN tendrils. Heterologous overexpression of VvFUL-L in arabidopsis promoted early flowering and reduced inflorescence branching, suggesting its potential role in regulating lateral meristem development and affecting tendril formation. Collectively, these findings establish that Hormone Signaling, particularly cytokinin-GA crosstalk, and MADS-box regulators, such as VvFUL-L, are key regulators of inflorescence versus tendril growth in grapevines, providing a basis for future molecular and breeding studies.

Vitis↗

PubMed2026

ARISE: RNA-anchored shared-edge topology and hierarchical fusion for spatial multi-omics integration.

MOTIVATION: Spatial multi-omics technologies jointly profile transcriptomes, proteins and chromatin accessibility in situ, enabling integrative analysis of tissue organization across molecular layers. However, most existing graph-based integration methods rely on independently constructed modality-specific k-nearest-neighbor graphs. When auxiliary modalities are sparse or noisy, these graphs can become topologically discordant, propagate spurious edges, weaken cross-modal alignment, and reduce spatial domain resolution. RESULTS: We present Anchored RNA for Integrated Spatial Embedding (ARISE), an RNA expression anchored framework for spatial multi-omics integration. ARISE defines a shared-edge topology by intersecting RNA feature-similarity and spatial-proximity graphs, encodes auxiliary modalities on this common scaffold, and integrates them through inside-out hierarchical fusion. We further show theoretically that graph intersection minimizes false-positive edges within a broad class of k-of-r graph fusion rules, providing a principled basis for topology anchoring. Across various spatial multi-omics benchmarks spanning simulated and real datasets in bi-modal and tri-modal settings, ARISE improves spatial domain identification, cross-modal consistency, and preservation of tissue structure relative to existing methods. Furthermore, the learned representation supports biologically meaningful downstream analyses, including marker-based domain annotation, pathway enrichment, and cis-regulatory inference, indicating that ARISE yields a robust and interpretable framework for spatial multi-omics integration. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/XiangxiangWang-code/ARISE. The archived version used in this study is available at https://doi.org/10.6084/m9.figshare.32686137.v2.

Multiomics↗

PubMed2025

Stereo-cell: Spatial enhanced-resolution single-cell sequencing with high-density DNA nanoball-patterned arrays.

Single-cell sequencing technologies have advanced our understanding of cellular heterogeneity and biological complexity. However, existing methods face limitations in throughput, capture uniformity, cell size flexibility, and technical extensibility. We present Stereo-cell, a spatial enhanced-resolution single-cell sequencing platform based on high-density DNA nanoball (DNB)-patterned arrays, which enables scalable and unbiased cell capture at a wide input range and supports high-fidelity transcriptome profiling. Stereo-cell further allows integration with imaging-based modalities and multiomics strategies, including immunofluorescence and epitope profiling. This platform is also compatible with profiling extracellular vesicles, microstructures, and large cells, whereas its spatial resolution facilitates in situ analysis of cell-cell interactions, cellular microenvironments, and subcellular transcript localization. Together, Stereo-cell provides a flexible framework for expanding single-cell research applications.

Animals↗

PubMed2026

Spatiotemporal transcriptomic analysis during cold ischemic injury to the murine kidney reveals compartment-specific changes.

BACKGROUND: Kidney transplantation is the preferred treatment strategy for end-stage kidney disease. Deceased donor kidneys usually undergo cold storage until kidney transplantation, leading to cold ischemia injury that may contribute to poor graft outcomes. However, the molecular characterization of potential mechanisms of cold ischemia injury remains incomplete. RESULTS: To bridge this knowledge gap, we leverage 10x Visium spatial transcriptomic technology to perform full transcriptome profiling of murine kidneys subject to varying durations of cold ischemia typical in a deceased donor kidney transplant setting. We develop a computational workflow to identify and compare spatiotemporal transcriptomic changes that accompany the injury pathophysiology in a tissue compartment-specific manner. We identify proportional enrichment of oxidative phosphorylation (OXPHOS) genes with increasing duration of cold ischemia injury within the oxygen-lean inner medulla region, suggestive of atypical metabolic presentation. This is distinct in cold ischemia injury tissue compared to warm ischemia-reperfusion kidney injury tissue. Spatiotemporal trends are validated by qPCR and immunofluorescence in a larger cohort of mice. CONCLUSIONS: Altogether, our spatiotemporal transcriptomic analysis identifies coordinated molecular changes within metabolic pathways such as OXPHOS deep within the cold ischemic kidney, highlighting the need for increased attention to the inner medulla and potential opportunities for new insights beyond those available from superficial biopsy-focused tissue examination.

Animals↗

PubMed2026

Four-dimensional molecular mapping from a spatial snapshot reveals the dynamics of hair follicle organogenesis.

Understanding organ formation requires capturing molecular information simultaneously in three-dimensional (3D) space and across developmental time. To this end, we developed 3D DNase-Enhanced Expression Profiling (3DEEP), a tissue-clearing approach that removes genomic DNA to extend spatial transcriptomic profiling hundreds of microns into intact tissues. We applied 3DEEP to neonatal mouse skin, capturing hundreds of developing hair follicles across their organogenesis trajectory. Ordering follicles by molecularly inferred developmental age transformed this single spatial snapshot into a four-dimensional (3D + time) molecular map of organogenesis. This map revealed developmental dynamics spanning stem cell compartment stratification, emergence of new cell subtypes within the follicle, and cascading structural transformations leading to hair canal formation. Comparative analysis of Foxn1-deficient nude mice, a hairlessness model, revealed organ-wide changes in developmental dynamics, including delayed molecular progression, reduced coordination, and increased developmental instability, preceding overt structural defects. This work demonstrates how deep-tissue spatial transcriptomics can uncover hidden dynamics of organ formation.

Animals↗

PubMed2026

Live-cell transcriptomics with engineered virus-like particles.

Transcriptomic profiling is widely applied to characterize cellular gene expression, yet existing approaches lyse cells and preclude direct analysis of transcriptional dynamics in the same sample over time. We addressed this limitation by engineering mammalian cells to "self-report" their transcriptional states via mRNA export in virus-like particles (VLPs). Repeated sampling of culture media from VLP-producing cell populations faithfully captured evolving transcriptional states in complex biological settings, including acute inflammatory stimulation of primary cell spheroids and multi-day differentiation of pluripotent stem cells. We engineered VLP components for multiplexed readouts from distinct cell types in co-culture and for tuning self-reported RNA profiles. Finally, we demonstrated the unique utility of self-reporting for selective longitudinal tracking of endothelial cell dynamics within the enclosed architecture of a microphysiological co-culture system to identify perivascular stroma-dependent temporal gene programs underlying vasculogenesis. Altogether, this work establishes cellular self-reporting as a broadly enabling technology for live-cell transcriptome-wide gene expression profiling.

RNA↗

PubMed2026

Transcriptomics reveals species-specific adaptive strategies to calorie restriction in two Argopecten scallops with distinct lifespans.

Calorie restriction (CR) is a well-established non-genetic intervention for lifespan extension in multiple model organisms. Seasonal food shortage in cold and temperate seas may mimic CR, inducing in bivalves a response similar to that in vertebrates and thereby prolonging life expectancy. However, the relationship and the mechanism underlying the food availability and lifespan in bivalves remain largely unexplored. Two closely related scallop species the short-lived warm-water Argopecten irradians (lifespan <2 years) and the longer-lived cold-water Argopecten purpuratus (7-10 years) provide an ideal comparative system to investigate species-specific adaptive strategies. In this study, we subjected both species to CR for 30 and 56 days and performed comparative transcriptomic profiling, weighted gene co-expression network analysis (WGCNA), and physiological assays to elucidate their distinct molecular responses. Transcriptomic analysis revealed that A. purpuratus exhibited substantially more DEGs than A. irradians at both time points under CR, with both species showing downregulation of metabolic pathways but to different extents. A. irradians mounted an early nutrient-sensing response at 30 days (IGF1R, PIK3R3, INSR suppression), indicating acute sensitivity to limitation; by contrast, A. purpuratus displayed delayed FoxO activation at 56 days, along with its downstream effectors NFKBIA, CREB3L4, and SMAD4, suggesting a gradual adaptive program may link to its extended lifespan. WGCNA identified three negatively correlated modules in each species, with coral2 being the most prominent in A. irradians and darkolivegreen in A. purpuratus. The former was dominated by ciliary motility genes, whereas the latter featured coordinated repression of oxidative phosphorylation. Additionally, both species exhibited conserved suppression of mTOR/S6K growth signaling and activation of cellular maintenance programs. Collectively, these findings expand the understanding of CR-mediated longevity regulation in bivalves and provide candidate gene resources for future functional studies and breeding programs.

Pectinidae↗

PubMed2026

Mycosis Fungoides-Like Atopic Dermatitis Represents a Th22-Dominant Inflammatory Endotype.

BACKGROUND: Early-stage mycosis fungoides (MF) often presents diagnostic challenges because of its clinical overlap with atopic dermatitis (AD). In clinical practice, we encountered a subset of patients with severe AD who fulfilled the MF diagnostic criteria yet remained clinically indistinguishable from AD and presented refractoriness to advanced therapies. We termed this ambiguous entity "mycosis fungoides-like AD" (mfAD) and sought to determine whether it represents malignant transformation or a distinct inflammatory endotype of AD. METHODS: Skin biopsies were obtained from 7 patients with AD and 11 patients with mfAD. We performed paired single-cell RNA sequencing and single-cell T-cell receptor sequencing analyses. Publicly available MF and AD datasets were integrated for comparative analysis. Spatial transcriptomic profiling was used to contextualize single-cell findings within the tissue architecture. RESULTS: Comparative transcriptomic analysis revealed that T cells in mfAD were aligned with those in AD and lacked genomic instability. High-resolution profiling showed that mfAD was characterized by oligoclonal Th22 expansion rather than a single dominant malignant clone. Notably, all patients with mfAD achieved rapid clinical remission with selective JAK1 inhibition, indicating the therapeutic response characteristics of inflammatory dermatoses. CONCLUSION: Our findings demonstrate that mfAD is not a true malignancy, but rather a Th22-driven inflammatory endotype of AD. These results redefine mfAD as an inflammatory subtype within the AD spectrum, providing a mechanistic explanation for both the "pseudo-monoclonality" that leads to MF misdiagnosis and the failure of dupilumab. This study establishes a rationale for the use of JAK inhibitors in precision medicine for this patient population.

JAK inhibitor↗

PubMed2026

Disease-driven post-transcriptional alterations and alternative splicing in podocytes in focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and progression to end-stage renal disease, yet its molecular pathogenesis remains still incompletely defined. While transcriptional alterations in podocytes have been extensively characterized, the contribution of post-transcriptional regulatory mechanisms is poorly understood. Here, we combined a zebrafish podocyte-specific injury model with glomerulus-resolved transcriptomic profiling to dissect RNA regulatory alterations during FSGS progression. Integrated analyses of bulk RNA sequencing, small RNA profiling, and alternative splicing revealed pronounced, time-dependent remodeling of the glomerular transcriptome. We demonstrate that podocyte injury is associated with loss of key podocyte-specific proteins, activation of inflammatory pathways, remodeling of the extracellular matrix, and altered microRNA expression, such as miR-21 and miR-193. Moreover, we found that alternative splicing influences key podocyte gene expression, affecting genes critical for slit diaphragm integrity, actin cytoskeleton organization, and glomerular basement membrane stability. Isoform analyses identified FSGS-associated isoform switches in SRSF3 and EPB41L5. Importantly, these changes were also evident in glomeruli from FSGS patients, demonstrating that the zebrafish model recapitulates key molecular features of human disease and highlighting alternative splicing as a central regulatory mechanism in FSGS.

Animals↗