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Single-cell RNA-sequencing reveals the transcriptional landscape of lacrimal gland in GVHD mouse model.
PURPOSE: To investigate the global transcriptional landscape of lacrimal gland cell populations in the GVHD mouse model. METHODS: Single-cell RNA sequencing and further bioinformatic analysis of dissociated lacrimal gland (LG) cells from the mouse model were performed. Parts of transcriptional results were confirmed by immunofluorescence staining. RESULTS: We identified 23 cell populations belonging to 11 cell types. In GVHD LG, the proportion of acinar cells, myoepithelial cells, and endothelial cells was remarkably decreased, while T cells and macrophages were significantly expanded. Gene expression analysis indicated decreased secretion function, extracellular matrix (ECM) synthesis, and increased chemokines of myoepithelial cells. A newly described epithelial population named Lrg1high epithelial cells, expressing distinct gene signatures, was exclusively identified in GVHD LG. The fibroblasts exhibited an inflammation gene pattern. The gene pattern of endothelial cells suggested an increased ability to recruit immune cells and damaged cell-cell junctions. T cells were mainly comprised of Th2 cells and effective memory CD8+ T cells. GVHD macrophages exhibited a Th2 cell-linked pattern. CONCLUSIONS: This single-cell atlas uncovered alterations of proportion and gene expression patterns of cell populations and constructed cell-cell communication networks of GVHD LG. These data may provide some new insight into understanding the development of ocular GVHD.
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Role of cancer stem cell heterogeneity in intrahepatic cholangiocarcinoma.
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly invasive bile duct cancer with poor prognosis due to frequent recurrence and limited effective treatments. Cancer stem cells (CSCs) contribute to ICC's therapeutic resistance and recurrence, driven by distinct cellular subpopulations with variable tumorigenic properties. Recent advances in single-cell RNA sequencing (scRNA-seq) have enabled a deeper exploration of cellular heterogeneity in tumors, offering insights into unique CSC subgroups that impact ICC progression and patient outcomes. This study aimed to investigate the effect of CSC heterogeneity on the prognosis of ICC. METHODS: The scRNA-seq dataset GSE142784 was retrieved from the Gene Expression Omnibus (GEO) database, and Bulk RNA-seq data were obtained from The Cancer Genome Atlas (TCGA) databases. Hallmarks and AUCell R package were adopted for analyzing the signaling pathway activity, CellChat for observing cell communication between subgroups, and SCENIC for analyzing transcription factors expression. The immune cell infiltration and drug sensitivity of the model were analyzed using the CIBERSORT algorithm and the "pRRophetic" R packages, respectively. And immunohistochemistry (IHC) tests were used to evaluate expression of transcription factors in ICC patients. RESULTS: Based on scRNA-seq data, five clusters (DLK+, CD13+, CD90+, CD133+, and other cholangiocarcinoma cells) were observed in ICC, which presented different signaling pathway activities, such as HSF1 and STAT1 were highly expressed in the CD133 cluster, and consistent with the results of IHC tests. Pathways like Notch and Wnt/β-catenin signaling transferred among above subgroups. Further, subgroups favored varied immune response and drug sensitivity, and CD133+ subgroup patients showed significantly shortened recurrence-free survival (RFS). CONCLUSIONS: Configuring the subgroup of ICC is helpful for predicting the prognosis and drug resistance in ICC and can provide new strategies for cancer treatment.
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Stress-free single-cell transcriptomic profiling and functional genomics of murine eosinophils.
Eosinophils are a class of granulocytes with pleiotropic functions in homeostasis and various human diseases. Nevertheless, they are absent from conventional single-cell RNA sequencing atlases owing to technical difficulties preventing their transcriptomic interrogation. Consequently, eosinophil heterogeneity and the gene regulatory networks underpinning their diverse functions remain poorly understood. We have developed a stress-free protocol for single-cell RNA capture from murine tissue-resident eosinophils, which revealed distinct intestinal subsets and their roles in colitis. Here we describe in detail how to enrich eosinophils from multiple tissues of residence and how to capture high-quality single-cell transcriptomes by preventing transcript degradation. By combining magnetic eosinophil enrichment with microwell-based single-cell RNA capture (BD Rhapsody), our approach minimizes shear stress and processing time. Moreover, we report how to perform genome-wide CRISPR pooled genetic screening in ex vivo-conditioned bone marrow-derived eosinophils to functionally probe pathways required for their differentiation and intestinal maturation. These protocols can be performed by any researcher with basic skills in molecular biology and flow cytometry, and can be adapted to investigate other granulocytes, such as neutrophils and mast cells, thereby offering potential insights into their roles in both homeostasis and disease pathogenesis. Single-cell transcriptomics of eosinophils can be performed in 2-3 d, while functional genomics assays may require up to 1 month.
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The evolution of facultative symbiosis in stony corals.
Most stony corals are obligate symbionts that are dependent on nutrients provided by the photosynthetic activity of dinoflagellates residing within specialized cells1. Disruption of this symbiotic consortium leads to coral bleaching and, ultimately, mortality2. However, a few coral species exhibit facultative symbiosis, allowing them to survive extended periods of bleaching3,4. Despite this resilience, the underlying biological mechanisms remain poorly understood. Here we investigate the genomic and cellular basis of facultative symbiosis in Oculina patagonica, a thermotolerant Mediterranean coral5,6. We sequenced and annotated a chromosome-scale genome of O. patagonica and built cell atlases for this species and two obligate symbiotic corals. Comparative genomic analysis revealed karyotypic and syntenic conservation across all scleractinians, with species-specific gene expansions primarily driven by tandem duplications. Single-cell transcriptomic profiling of symbiotic and naturally aposymbiotic wild specimens identified an increase in phagocytic immune cells and a metabolic shift in gastrodermal gene expression from growth-related functions to quiescent, epithelial-like states. Cross-species comparison of host cells uncovered Oculina-specific metabolic and signalling adaptations indicative of an opportunistic, dual-feeding strategy that decouples survival from symbiotic state.
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Multi-omics joint analysis and identification of candidate genes for the rate of right ovarian degeneration in geese.
Avian species exhibit a notable asymmetry in their reproductive systems, with the left ovary maturing into a functional organ and the right ovary degenerating. This asymmetry is widespread across bird species, yet the molecular underpinnings of right ovarian degeneration are not fully understood. In this study, we constructed a cellular atlas of the degenerating right ovary in geese through single-cell transcriptome sequencing (scRNA-seq), revealing distinct cellular compositions and gene expression profiles. Meanwhile, we identified variations in the rate of right ovarian degeneration among individuals, which may influence the gene expression profiles of the hypothalamic-pituitary-ovary (HPO) axis, particularly the related pathways involved in steroid hormone secretion and follicular development of the left ovary. Genomic sequencing combined with transcriptomic data, led to the identification of LHX9 and ARID5B as potentially associated with the rate of right ovarian degeneration in avian species. Our study provides a comprehensive cellular and molecular understanding of the degeneration process in the right ovary of geese. The identification of LHX9 and ARID5B as potential regulators of degeneration rate offers new insights into the genetic factors influencing avian reproductive asymmetry. These findings have implications for improving reproductive efficiency in geese and contribute to the broader understanding of the evolution of avian reproductive systems.
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Polystyrene nanoplastics disrupt ovarian development via cytoskeletal remodeling and epigenetic reprogramming particularly in granulosa cells.
Emerging environmental health issues posed by micro- and nanoplastics (M/NPs) have raised significant concerns. Accumulating evidence suggested that M/NPs can bioaccumulate in gonads and impair fertility in animals, yet the underlying cellular mechanisms and tissue-specific responses remain poorly understood. In this study, we employed in vivo and in vitro models to systematically investigate the impact of polystyrene micro- and nanoplastics (PS-M/NPs, 100 nm and 5 µm) on ovarian development and function in pubertal female mice. Following 35-day exposure, we observed size-dependent reproductive toxicity, with 100 nm PS-NPs causing reduced body weight gain and ovarian size, disrupted folliculogenesis, and altered hormone levels. Leveraging single-cell RNA-sequencing (scRNA-seq), we uncovered profound alterations in intracellular communication networks across seven ovarian cell types. Granulosa cells (GCs) were identified as the primary target of PS-NPs, exhibiting marked transcriptional changes, including dysregulation of FSCN1, a critical actin cytoskeleton regulator. In vitro experiments confirmed that only 100 nm PS-NPs were internalized by GCs, leading to cell cycle arrest, necroptosis, and hormonal dysfunction. Mechanistically, PS-NPs triggered F-actin cytoskeleton remodeling, increasing cell stiffness and histone modifications (H3K4me3, H3K27ac) associated with chromatin accessibility. Integrated ATAC-seq and RNA-seq analyses implicated STAT1 as a key transcriptional regulator driving PS-NP-induced epigenetic and transcriptional changes. Overall, our findings establish the first single-cell resolution atlas of PS-NP-mediated ovarian toxicity, revealing that NPs disrupt reproduction through cytoskeletal damage and epigenetic reprogramming. This work provides unprecedented insights into the molecular and epigenetic consequences of M/NPs in mammalian reproduction, emphasizing the potential health risks of environmental M/NP exposure.
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Single-cell transcriptomic landscape of the southern green stink bug (Nezara viridula) midgut.
BACKGROUND: The southern green stink bug (SGSB), Nezara viridula, is a globally distributed hemipteran pest that damages many economically important crops. Its midgut supports digestion, defense, symbiosis, and interactions with orally delivered control agents, yet the cellular composition of this tissue remains poorly characterized. We therefore developed a single-cell transcriptomic atlas of the N. viridula midgut. RESULTS: Single-cell RNA sequencing of two biological replicates yielded a quality-filtered data set of 13,763 cells. Unsupervised clustering identified 12 transcriptionally distinct populations with putative annotations, including a stem cell/enteroblast (SC/EB)-like population, seven enterocyte-related populations, goblet-like cells, enteroendocrine cells, visceral muscle cells, and an extracellular-matrix-associated epithelial population. Enterocyte-related populations accounted for more than 77% of recovered cells. Putative annotations were assigned primarily from marker gene enrichment and homology to markers reported in other insects. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified population-associated functional enrichment patterns, and pseudotime analysis suggested transcriptional relationships between the SC/EB-like population and several enterocyte- and secretory-associated populations without establishing developmental lineages. Immune- and defense-associated transcripts were preferentially enriched in the pEC2 population, and genes associated with symbiont recognition, insecticide action, xenobiotic transport, and orally delivered double-stranded RNA showed population-biased expression. Descriptive comparisons with published insect midgut data sets identified shared and data-set-specific patterns among annotated populations. CONCLUSION: This atlas provides the first single-cell transcriptomic resource for a stink bug midgut and establishes a descriptive cellular framework for SGSB midgut biology. The dataset prioritizes candidate genes and cell populations for future spatial validation, functional testing, and studies of hemipteran midgut physiology, symbiosis, immunity, and pest-management-relevant traits. © 2026 Society of Chemical Industry.
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Transcriptomic landscape of Marchantia polymorpha sexual organs at single-nucleus resolution.
Marchantia polymorpha, a model liverwort, provides a valuable system for investigating the evolution of plant sexual reproduction. To explore the cellular landscape of its reproductive structures, we generate a single-nucleus transcriptomic atlas of the antheridiophore, archegoniophore, and sporophyte. Using single-nucleus RNA sequencing (snRNA-seq), we capture over 30,000 high-quality nuclei and identify distinct cell populations. In the male organ, we characterize stages of spermatogenesis from early antheridium cells to mature sperm, revealing dynamic transcriptional programs including cell cycle regulation, chromatin remodeling, and calcium signaling. In the female organ, we define cell types including archegonial layers and secondary central cells. Sporophyte clusters are annotated as spores, elaters, capsule wall, foot, and seta cells, with transcriptional signatures related to structural support, stress response, and reproductive functions. Cross-species analysis indicates that capsule wall cells in liverworts are similar to tapetum cells. Notably, foot cells exhibit high expression of genes involved in sporopollenin biosynthesis and signaling pathways, serving as a central hub that mediates communication between the maternal gametophyte and the developing sporophyte. This study provides a comprehensive cellular and molecular map of M. polymorpha reproductive organs and sporophyte, establishing a framework for investigating the development and evolution of sexual reproduction in early land plants.
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Single-cell transcriptomics identifies PRDX1 and GPX4 as potential ferroptosis regulators and tumor microenvironment--related molecules in hepatocellular carcinoma.
The present study aimed to investigate the expression and roles of peroxiredoxin 1 (PRDX1) and glutathione (GSH) peroxidase 4 (GPX4) in ferroptosis regulation and the tumor microenvironment in hepatocellular carcinoma (HCC). The expression levels of PRDX1 and GPX4 were assessed in HCC through analysis of datasets from The Cancer Genome Atlas (TCGA), GSE14520 from the Gene Expression Omnibus database and the Human Protein Atlas, along with HCC cell lines. Diagnostic and prognostic values were evaluated using receiver operating characteristic curves and Kaplan-Meier survival analyses. The single-cell dataset GSE149614 was employed to investigate the cellular localization and characteristics of specific cell subpopulations expressing PRDX1 or GPX4 within the HCC tumor microenvironment. The relationships between PRDX1, GPX4 and ferroptosis-related pathways were explored using the FerrDb database and Gene Set Enrichment Analysis. Additionally, their interactions with the immune microenvironment were examined utilizing the CIBERSORT algorithm. To validate the results of the bioinformatics analysis, the present study utilized small interfering (si)RNA technology to construct single gene knockdown and dual gene co-knockdown models targeting PRDX1 and GPX4 in Hep3B cells. Subsequently, the proliferative activity of each group of cells was evaluated using the Cell Counting Kit-8 method and the levels of the intracellular lipid peroxidation product malondialdehyde (MDA) were detected using the MDA detection kit. The results of the present study demonstrated that the expression levels of PRDX1 and GPX4 were upregulated in HCC tissues and cell lines. The area under the curve for the combined diagnostic model of PRDX1 and GPX4 in HCC was 0.83. Furthermore, elevated expression levels of PRDX1 or GPX4 predicted reduced overall survival (OS), and their expression was weakly positively correlated in HCC. Single-cell transcriptomics demonstrated predominant expression of both genes in malignant cells. GPX4 was primarily detected in early-differentiation subgroups enriched in metabolic and ferroptosis pathways, whereas PRDX1 was predominantly expressed in intermediate-differentiation subgroups associated with antioxidative stress pathways. The dual-high PRDX1/GPX4 expression group exhibited increased reactive oxygen species, GSH and iron levels, whereas the dual-low group had prolonged OS. Immune infiltration analysis indicated a trend of higher M0 macrophage levels and lower CD4+ T-cell counts in the dual-high expression group. Furthermore, PRDX1 expression was positively correlated with multiple immune checkpoint genes, whereas GPX4 expression was markedly negatively correlated only with CD274 and TIGIT. The siRNA-PRDX-1/siRNA-GPX4-1 group exhibited significantly inhibited HCC cell proliferation and promoted MDA production; however, proliferative activity was partially increased compared with that in the siRNA-PRDX-1 group, whereas the levels of MDA accumulation were significantly reduced compared with in the siRNA-GPX4-1 group. In conclusion, the current study revealed the concerted co-expression of PRDX1 and GPX4 in malignant HCC, which was associated with ferroptosis evasion and immune suppression. Furthermore, the present findings suggested that PRDX1 may shift from an antioxidant to a pro-oxidant mediator under GPX4 deficiency, thereby alleviating lipid peroxidation. These findings support targeting this axis as a future therapeutic breakthrough.
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EDEM2 is a diagnostic and prognostic biomarker and associated with immune infiltration in glioma: A comprehensive analysis.
Glioma is a highly common pathological brain tumor. Misfolded protein response, which is strongly associated with the growth of cancerous tumors, is mediated by the gene, endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2. However, this gene has not been linked to glioma. To assess the same, we used The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Genotype-Tissue Expression datasets. The gene was overexpressed in gliomas. This overexpression was linked to unfavorable clinical characteristics, such as the World Health Organization grade, isocitrate dehydrogenase mutation, and the combined loss of the short arm chromosome 1 and the long arm of chromosome 19. Quantitative polymerase chain reaction experiments and immunohistochemistry on clinical samples from our institution verified the gene's expression and clinical importance. The Human Protein Atlas website verified the messenger ribonucleic acid expression of the gene in glioma cell lines, and immunohistochemistry verified the presence of its protein. A previous survival study indicated that its high expression is substantially related to a bad prognosis. It was identified as an independent predictor of primary glioma prognosis using multivariate Cox regression analysis. To forecast individual survival, we created a nomogram based on this (concordance-index = 0.847). Additionally, functional annotation demonstrated its major role in the control of the extracellular matrix and immune system. The scratch assay and transwell migration assay confirmed the decreased invasive ability of U251 glioma cells with the gene knockdown. Its increased expression was found to be related to the extent of macrophage infiltration using the CIBERSORT, ESTIMATE, Single-sample Gene Set Enrichment Analysis, and Tumor Immune Single-Cell Hub (TISCH) algorithms. The Tumor Immune Dysfunction and Exclusion algorithm revealed that the gene can accurately predict the response of immunotherapy (area under the receiver operating characteristic curve = 0.857). Further, isocitrate dehydrogenase 1 mutation is typically more frequent when the gene expression is high. Finally, five medicines targeting this gene were discovered utilizing the molecular docking program and drug sensitivity analysis of the RNAactDrug website. Low expression of the gene inhibited glioma cell invasion. Therefore, the gene is helpful for the diagnosis, prognosis, and case-specific immunotherapy of glioma.