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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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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.
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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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Integrated single-cell and bulk RNA sequencing analysis reveals ACACA as a potential prognostic and immunotherapeutic biomarker across cancers.
BACKGROUND: Acetyl-CoA carboxylase alpha (ACACA), a crucial rate-limiting enzyme governing de novo biosynthesis of fatty acids, drives oncogenic metabolic reprogramming in diverse malignancies. However, the multiomics investigation and immunological implications of ACACA across cancers remain unclear. METHODS: We performed a comprehensive pan-cancer analysis of ACACA via transcriptomic, proteomic, and clinical data from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA) databases. Then, single-cell RNA sequencing acquired from the Gene Expression Omnibus (GEO) database was employed to map the expression pattern of ACACA in the tumor microenvironment (TME). Subsequently, functional validation experiments were conducted in lung cancer and sarcoma cells. RESULTS: High ACACA expression was associated with poor survival in various cancers, particularly those exhibiting dysregulated lipid metabolism. Immune profiling revealed that elevated ACACA expression was associated with low infiltration of CD8+ T cells and activated natural killer (NK) cells. Single-cell analysis of lung adenocarcinoma revealed that ACACA was expressed predominantly within malignant cells and contributed to an immunosuppressive microenvironment through migration inhibitory factor (MIF) signaling and the extracellular matrix (ECM) remodeling pathway. Furthermore, in vitro studies demonstrated that ACACA inhibition suppresses fatty acid synthesis and tumor growth in lung cancer and sarcoma cells. CONCLUSIONS: Our study establishes ACACA as a key metabolic regulator that links lipid metabolism to immune evasion and drug resistance, highlighting its potential as a promising therapeutic target across cancers.
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An integrated single-cell lung cancer atlas reveals distinct fibroblast phenotypes between adenocarcinoma and squamous cell carcinomas.
The tumor microenvironment (TME) not only influences cancer progression but also has been shown to have a significant effect on the prognosis. One of the major TME components is cancer-associated fibroblasts (CAFs), of which several subtypes have been identified in tumor tissues. Although single-cell RNA sequencing (scRNA-seq) technology is a powerful tool for investigating the proportions and composition of cells in tissues, large-scale datasets are needed to analyze small cell populations. Here, we constructed an integrated scRNA-seq dataset for non-small cell lung cancer (NSCLC) by compiling publicly available data and observed differences in TME heterogeneity and cellular composition between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In particular, we identified significant differences in CAF subtypes between LUAD and LUSC. Inflammatory CAFs (iCAFs) were predominantly found in LUAD, whereas myofibroblastic CAFs (mCAFs) were more common in LUSC. A coculture analysis of lung fibroblasts confirmed that LUAD cells induced the iCAF phenotype and, in contrast, that LUSC cells promoted myofibroblastic differentiation. A correlation analysis with the prognosis identified mCAFs as poor prognostic factors in both LUAD and LUSC, but iCAFs were found to be a poor prognostic factor only in LUSC, with the opposite pattern observed in LUAD. This work highlights important considerations regarding the CAF subtype dominance in LUAD and LUSC, which may be related to the prognosis.
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Human Cell Aging Transcriptome Atlas (HCATA): a single-cell atlas of age-associated transcriptomic alterations across human tissues.
Biological aging is associated with progressively more severe genetic and epigenetic alterations. While these changes are expected to affect the transcriptional profile of cells, the magnitude of that effect is unknown as the aging transcriptome is still poorly understood. Understanding the aging transcriptional landscape will give us greater insight into how cells are affected by and/or respond to the aging process. To facilitate the large-scale exploration of the aging transcriptome, we report the development of the Human Cell Aging Transcriptome Atlas (HCATA). HCATA, contains single-cell RNA-sequencing datasets from 76 publications totaling 92 million cells and 3,475 tissue-level samples across more than 50 tissue types with ages ranging from 0 to 103 years. HCATA includes a genome browser that allows users to interactively explore age-related differential expression, as well as functions to explore related pathways at the tissue and cell-type level. HCATA is publicly accessible at http://hcata-xiaodonglab.org:3304 .
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A high-resolution atlas of the brain predicts lineage and birth order underlying neuronal identity.
Gene expression shapes the nervous system at every biological level, from molecular and cellular processes defining neuronal identity and function to systems-level wiring and circuit dynamics underlying behavior. Here, we generate the first high-resolution, single-cell transcriptomic atlas of the adult Drosophila melanogaster central brain by integrating multiple datasets, achieving an unprecedented 10-fold coverage of every neuron in this complex tissue. We show that a neuron's genetic identity overwhelmingly reflects its developmental origin, preserving a genetic address based on both lineage and birth order. We reveal foundational rules linking neurogenesis to transcriptional identity and provide a framework for systematically defining neuronal types. This atlas provides a powerful resource for mapping the cellular substrates of behavior by integrating annotations of hemilineage, cell types/subtypes, and molecular signatures of underlying physiological properties. It lays the groundwork for a long-sought bridge between developmental processes and the functional circuits that give rise to behavior.