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Canine mesenteric lymph nodes (MLNs) characterization by sc-RNAseq: insights compared to human and mouse MLNs.
In the human and veterinary fields, oral vaccines generate considerable interest. In dogs, these vaccines are newly developed, and understanding their mechanisms is crucial. Mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) are important sites for gastrointestinal mucosal induction, yet canine MLNs lack sufficient information. To address this, we collected MLN samples from healthy dogs, performed flow cytometry to characterize immune cells, and conducted single-cell RNA sequencing (scRNA-seq) to explore subpopulations, particularly B and T lymphocytes. This effort enabled the characterization of canine MLN's main cell populations and the construction of a predictive atlas, as well as the identification of particularities of this area.
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scRNA-seq and proteomics reveal the distinction of M2-like macrophages between primary and recurrent malignant glioma and its critical role in the recurrence.
AIMS: Tumor-associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2-like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence. METHODS: We employed single-cell RNA sequencing to construct a single-cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma. RESULTS: Six subgroups of TAMs were annotated and M2-like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up-regulation of several cancer pathways and intercellular interaction-related genes are associated with the recurrence of malignant glioma. Moreover, the M2-like TAMs can activate the PI3K/Akt/HIF-1α/CA9 pathway in the malignant glioma cells via SPP1-CD44-mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance. CONCLUSION: Our study uncovers the distinction of M2-like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma.
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Comprehensive insights into the development of arabidopsis trichomes by single-nucleus RNA-seq.
BACKGROUND: Trichomes are specialized epidermal structures that perform critical functions in plant defense and development. Despite their importance, the molecular programs governing trichome initiation, differentiation, maturation, and complete developmental progression remain incompletely characterized, largely due to the inherent limitations of conventional bulk RNA sequencing approaches in capturing cellular heterogeneity. To address this knowledge gap, we leveraged publicly available single-nucleus RNA sequencing (snRNA-seq) data from Arabidopsis thaliana to construct a high-resolution developmental trajectory of trichomes, encompassing the transition from epidermal cells through initiation to branching stages. This approach enabled us to identify stage-specific transcriptional regulators and refine the molecular framework underlying trichome development. RESULTS: We successfully reconstructed a continuous developmental trajectory of arabidopsis trichomes and identified distinct stages characterized by extensive transcriptional reprogramming. Key regulatory genes, including VILLIN 1(VLN1), exhibited strong stage-specific expression during the initiation phase. Additionally, multiple long non-coding RNAs (lncRNAs) were found to be differentially expressed across developmental stages, suggesting potential roles in early lineage specification and trichome fate commitment. CONCLUSIONS: This study presents a high-resolution single-nucleus transcriptomic atlas of Arabidopsis trichome development, spanning the continuum from epidermal cells to trichome branching stages, and establishes a comprehensive molecular framework delineating the complete developmental trajectory. This resource provides valuable genetic insights for future functional investigations.
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Novel Copper-Responsive Cell Subtypes in Oyster Gills: scRNA-Seq Uncovers Detoxification Strategy and Intraspecific Accumulation Variation.
As a critical interface for metal hyperaccumulation, the multicellular complexity of oyster gills poses a challenge in studying their metal uptake and detoxification mechanisms. Here, we constructed the first cell atlas of oyster gills at single-cell resolution level, identifying a total of 18 cell types. Single-cell transcriptomic analysis of gills from oysters with high and low Cu accumulation revealed the cellular regulatory network underlying intraspecific differences in metal accumulation. For the first time, Cu-specific accumulating copperphilic cells in the oyster gills were identified, and a direct correlation was confirmed between copperphilic cell abundance and Cu content (R2 = 0.92). Trajectory analysis of cell differentiation revealed stage-specific gene module switching in metal-related cells, in which oxidative stress responses were activated in the early phase, while ion transport regulation dominated in the mature phase. Differentiation of Cu accumulation efficiency was mainly influenced by neuroendocrine-immune cells in gills maintaining physiological homeostasis, copperphilic cells selectively silencing intercellular communication, as well as ionocyte-mediated ncWNT pathway reprogramming. These results indicate a synergistic strategy by which oyster gills with high Cu accumulation enhance stress pathways (e.g., LT/RANKL) to mitigate Cu toxicity. This study provides a single-cell framework for studying the environmental adaptation and bioaccumulation mechanisms of pollutants.
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TMEM106C, BSG, COPE, CDCA8, KPNA2, LIG1, UQCRH, and CCT5: Predictive of Survival and Immunotherapy Resistance in Hepatocellular Carcinoma.
INTRODUCTION: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with cellular senescence playing a context-dependent role in tumor progression and the immunosuppressive microenvironment. This study is aimed at identifying senescence-related gene signatures through integrated single-cell and transcriptomic analyses to construct a robust prognostic model for predicting survival and immunotherapy response in HCC patients. METHODS: We obtained single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database and transcriptomic data from The Cancer Genome Atlas (TCGA). The scRNA-seq data were processed using the Seurat and Harmony packages for cell clustering and batch correction. Senescence scores were calculated via the AUCell package, and differentially expressed genes were identified using the limma package. Prognostic genes were selected through univariate and LASSO Cox regression (glmnet package) to construct a risk model, which was validated in multiple independent cohorts. Immune infiltration was assessed with single-sample gene set enrichment analysis (ssGSEA), TIMER, and MCPCounter algorithms, and response to immune checkpoint blockade was predicted using the tumor immune dysfunction and exclusion (TIDE) platform. Experimental validation included qRT-PCR, Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays in HCC cell lines. RESULTS: A total of 80,997 identified cells were allocated to eight clusters, with an evidently higher percentage of natural killer (NK) cells in HCC samples. A higher senescence score was also seen in HCC samples, and poor prognosis was noticed in the patients of high senescence score group. Further, the DEGs were intersected with the genes highly expressed in Population 4 of NK cells to reveal their enrichment in cell cycle and cell division. Further, eight genes (TMEM106C, BSG, COPE, CDCA8, KPNA2, LIG1, UQCRH, and CCT5) with differential expression in HCC were applied to construct the risk model, which could stratify HCC patients into different risks and predict the prognosis. Besides, the high immune infiltration and expression levels of immune checkpoint-relevant genes yet poor immunotherapy response were noticed in HCC patients of high risk. Further validation tests have suggested that the knockdown of CDCA8 repressed the malignant phenotypes of HCC cells. DISCUSSION: This integrated analysis establishes a senescence-related gene signature as a robust tool for prognostic stratification and immunotherapy response prediction in HCC. The model highlights the complex interplay between cellular senescence and the immunosuppressive tumor microenvironment, offering insights for personalized treatment strategies. Furthermore, the identified biomarker CDCA8 represents a promising therapeutic target warranting further investigation. CONCLUSION: These discoveries provide novel evidence on senescence in HCC, which may tailor the pharmacological interventions to improve the clinical management.
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Single-cell multi-omics dissects transcript isoform and immune repertoire dynamics in human immunosenescence.
Immunosenescence, a major hallmark of systemic aging, refers to the progressive functional decline of the immune system. This decline not only compromises host defense and immunological memory but also fuels chronic inflammation and tissue degeneration (collectively known as inflammaging). While single-cell RNA sequencing (scRNA-seq) has revealed transcriptomic alterations associated with immune aging, analyses restricted to transcript abundance fail to capture deeper regulatory layers, such as transcript isoform diversity and the remodeling of immune receptor repertoires. To address this limitation, we present a human peripheral immune single-cell multi-omics atlas that integrates gene expression, transcript isoform diversity, and immune receptor repertoires. By combining single-cell full-length transcriptome sequencing (scCycloneSEQ), short-read scRNA-seq, and single-cell immune receptor sequencing (scTCR/BCR-seq), we systematically profiled peripheral blood mononuclear cells (PBMCs) from healthy donors aged 30-40 and 60-70 years. Our analyses uncovered extensive age-related remodeling of immune cell composition, functional states, and TCR/BCR diversity. Notably, we found that CD4+ effector memory T cells exhibited widespread differential isoform usage (DIU), 3'UTR length variation, and a marked reshaping of cytotoxic T lymphocyte (CTL) clonotypes-all of which were closely associated with aging-related inflammation and cellular senescence. This multi-omics atlas delineates key molecular features of immunosenescence and provides a high-resolution resource for deciphering the regulatory architecture underlying immune aging.
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ScRNA-seq reveals dark- and light-induced differentially expressed gene atlases of seedling leaves in Arachis hypogaea L.
Although the regulatory mechanisms of dark and light-induced plant morphogenesis have been broadly investigated, the biological process in peanuts has not been systematically explored on single-cell resolution. Herein, 10 cell clusters were characterized using scRNA-seq-identified marker genes, based on 13 409 and 11 296 single cells from 1-week-old peanut seedling leaves grown under dark and light conditions. 6104 genes and 50 transcription factors (TFs) displayed significant expression patterns in distinct cell clusters, which provided gene resources for profiling dark/light-induced candidate genes. Further pseudo-time trajectory and cell cycle evidence supported that dark repressed the cell division and perturbed normal cell cycle, especially the PORA abundances correlated with 11 TFs highly enriched in mesophyll to restrict the chlorophyllide synthesis. Additionally, light repressed the epidermis cell developmental trajectory extending by inhibiting the growth hormone pathway, and 21 TFs probably contributed to the different genes transcriptional dynamic. Eventually, peanut AHL17 was identified from the profile of differentially expressed TFs, which encoded protein located in the nucleus promoted leaf epidermal cell enlargement when ectopically overexpressed in Arabidopsis through the regulatory phytohormone pathway. Overall, our study presents the different gene atlases in peanut etiolated and green seedlings, providing novel biological insights to elucidate light-induced leaf cell development at the single-cell level.
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Personalized single-cell transcriptomics reveals molecular diversity in Alzheimer's disease.
Alzheimer's disease (AD) is highly heterogeneous and driven by diverse molecular and cellular mechanisms. Functional genomics investigates these mechanisms from genetic variants to gene expression and regulation. We performed personalized functional genomics analysis on population-scale single-nucleus RNA-seq data, with cross-cohort validation across multiple cohorts comprising over 1900 individual brains, capturing donor-level cell type interactions and gene regulatory networks. Using a knowledge-guided graph neural network, we learned latent representations of each donor's functional genomics that accurately classified AD phenotypes, identified molecularly defined subpopulations, and traced disease progression trajectories. Our importance scores, derived from graph attentions, identified significant inter-donor differences and prioritized personalized cell type genes and regulatory networks. Finally, we identified gene regulatory QTLs (grQTLs) linking genetic variants to donor-level regulatory changes, providing insights into gene regulatory relationships beyond traditional eQTLs. All results are summarized into a personalized functional genomics atlas for AD, including an open-source framework, iBrainMap, for general use.
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scRNA-seq analysis reveals toxicity mechanisms in shrimp hemocytes subjected to nitrite stress.
In shrimp, hemocytes play an important role in detoxification and immune defense, and are where nitrite accumulates during exposure to this toxic environmental pollutant. However, the heterogeneity mechanisms of toxicity have not been reported under nitrite expose in shrimp. Here, we used single-cell RNA-seq to resolve 24,000 cells, which the responses of different cell populations of hemocytes under nitrite exposure in Penaeus vannamei. We identified 394 specific nitrite-responsive genes in 9 clusters of hemocytes, and found heterogeneity in the nitrite response of the three subpopulations of hemocytes (hyaline, semi-granular and granular cells). In hyaline, the response appeared modest, whereas nitrite-related dysregulation of metabolic processes in granular and semi-granular was pronounced. Ammonia nitrogen will rapidly accumulate in hemocytes of shrimp under nitrite stress. In semi-granular, excessive ammonia will interfere with oxidative phosphorylation and antioxidant system, thus inducing the production of reactive oxygen species. In granular, the abnormality of urea cycle caused by ammonia accumulation is the main toxic factor, which by inhibits arginase and arginine kinase. Collectively, our data provide a single-cell atlas for the dissection of shrimp hemocyte complexity, and reveal the toxicity mechanisms associated with nitrite exposure.
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Single-cell transcriptomics reveals dynamic cellular remodeling of porcine mammary gland during pregnancy.
Pregnancy elicits extensive remodeling of the mammary gland to establish the alveolar network required for lactation, yet the cellular programs underlying this transition in pigs remain poorly resolved. Here, we generated a single-cell transcriptomic atlas of the porcine mammary gland across gilt, late pregnancy, and post-lactational stages. Differential expression analyses identified epithelial, fibroblast and endothelial compartments as the most dynamic during pregnancy, motivating higher-resolution analyses of these lineages. Epithelial trajectories toward alveolar fate exhibited induction of fibrillar collagen programs, including COL1A1, COL3A1 and COL5A1, implicating epithelial contributions to extracellular matrix assembly. Fibroblast analysis revealed a PGLYRP1 + fibroblast subtype enriched for the chemokines CCL4, CCL5 and CCL21, suggesting a role in immune cell recruitment. Endothelial cells undergo stage-specific metabolic reprogramming, with late pregnancy characterized by increased expression of glycolysis-associated genes, including IGF1, FLCN and P2RX7, as well as lipid metabolism-related genes such as RBP7, KITLG and CD36. Cross-species comparison revealed conserved cellular identities and key molecular features ( ESR1, AR, FOXA1) across human, pig, and mouse mammary glands. Together, this atlas delineates the cellular logic underlying pregnancy-associated remodeling and serves as a resource for elucidating transcriptomic changes in the porcine mammary gland.