Your browser does not allow saving data (e.g. private mode): bookmarks will be lost when the tab closes.
Search PubMed
Keywords, author, journal, years — results from PubMed, abstracts with Russian translation, bookmarks in your browser.
Found: 4 939
Page 373 of 494-
Integrated multiomics analysis reveals the molecular features and crucial regulators of hair follicles in yak (Bos grunniens).
Yak is a unique bovine species that adapts to the extreme climate of the Qinghai-Tibet Plateau in part owing to its dense skin coat. Despite its essential role in cold adaptation, the genetic basis of hair follicle structure and growth has not been extensively studied in this iconic animal. In the present study, we construct a single-cell atlas of hair follicle (HF) cells from yak and taurine cattle and examine differences in their cellular composition and gene expression. Among the 14 cell types identified in HFs, the dermal papilla (DP) displays the most dramatic differences between cattle and yak. Detailed analysis reveals that the genes in the WNT signaling pathway are differentially expressed in the dermal papilla (DP) cells of yak. Using primary cultures of DP cells, we reveal that the inhibition or activation of WNT/β-Catenin dramatically alters cell cycle progression and autophagy. In complimentary with the ATAC-seq data, we show that SOX4 is directly associated with the promoters of WNT1 and WNT3A. Interestingly, increased autophagy regulates the expression of SOX4/WNT/β-Catenin to promote the proliferation of DP cells in yak. Together, these results reveal the molecular signature of coat adaptation at the single-cell transcription level and provide a new understanding of animal adaptation to extreme environments.
-
Dendritic Cell-Related Immune Marker CD1C for Predicting Prognosis and Immunotherapy Opportunities of Lung Adenocarcinoma Patients.
Lung adenocarcinoma (LUAD) is the most frequent type of lung cancer with a high mortality rate. Here, we aim to explore novel immune-related biomarkers for LUAD patients. Datasets, mRNA expression profiles, and clinical data concerned with LUAD were obtained from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), respectively. Differential expression analysis was performed to obtain differentially expressed genes (DEGs). Based on DEGs, we conducted functional enrichment analyses. Subsequently, Kaplan‑Meier (KM) was performed to analyze survival differences among different groups. Furthermore, immune cell infiltration proportion was calculated by CIBERSORT and TIMER. The relationship between gene and immune response was analyzed using Tumor Immune System Interactions (TISIDB) database. Finally, Pearson correlation analysis was performed between CD1C and six immune checkpoints. We identified dendritic cells (DCs)-related expression profiles from four LUAD samples. DCs' immune marker CD1C in LUAD was selected by univariate Cox regression analysis. Low CD1C expression patients had a poor prognosis. A total of 332 DEGs were identified in high and low CD1C expression groups, which primarily enriched in 348 GO terms and 30 KEGG pathways. There were significant differences in the infiltration proportion of 17 immune cells between high and low CD1C expression groups. Most immunomodulators, chemokines, and chemokine receptors were positively associated with CD1C expression. Six immune checkpoints were also positively correlated with CD1C expression. DCs related immunomarker CD1C probably plays a pivotal part in prognosis and immunotherapy of LUAD via a joint analysis of single-cell and bulk sequencing data.
-
ACKR3 in olfactory glia cells shapes the immune defense of the olfactory mucosa.
Barrier-forming olfactory glia cells, termed sustentacular cells, play important roles for immune defense of the olfactory mucosa, for example as entry sites for SARS-CoV-2 and subsequent development of inflammation-induced smell loss. Here we demonstrate that sustentacular cells express ACKR3, a chemokine receptor that functions both as a scavenger of the chemokine CXCL12 and as an activator of alternative signaling pathways. Differential gene expression analysis of bulk RNA sequencing data obtained from WT and ACKR3 conditional knockout mice revealed upregulation of genes involved in immune defense. To map the regulated genes to the different cell types of the olfactory mucosa, we employed biocomputational methods utilizing a single-cell reference atlas. Transcriptome analysis, PCR and immunofluorescence identified up-regulation of NF-κB-related genes, known to amplify inflammatory signaling and to facilitate leukocyte transmigration, in the gliogenic lineage. Accordingly, we found a marked increase in leukocyte-expressed genes and confirmed leukocyte infiltration into the olfactory mucosa. In addition, lack of ACKR3 led to enhanced expression and secretion of early mediators of immune defense by Bowman's glands. As a result, the number of apoptotic cells in the epithelium was decreased. In conclusion, our research underlines the importance of sustentacular cells in immune defense of the olfactory mucosa. Moreover, it identifies ACKR3, a druggable G protein-coupled receptor, as a promising target for modulation of inflammation-associated anosmia.
-
Multi-omics landscape analysis reveals the pan-cancer association of arginine biosynthesis genes with tumor immune evasion and therapy resistance.
BACKGROUND: The metabolism of arginine, a conditionally essential amino acid, plays a crucial role in cancer progression and prognosis. However, a more detailed understanding of the influence of arginine biosynthesis genes in cancer is currently unavailable. METHODS: We performed an integrative multi-omics analysis using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to determine the characteristics of these genes across multiple cancer types. To measure the overall activity of arginine biosynthesis genes in cancer, we calculated arginine biosynthesis scores based on gene expression. RESULTS: Our results indicated that the arginine biosynthesis score was negatively correlated with immune-related pathways, immune infiltration, immune checkpoint expression, and patient prognosis, and single-cell data further clarified that patients with high arginine biosynthesis scores showed a reduced proportion of T and B cells in an immune desert tumor microenvironment and were insensitive to immunotherapy. We also identified several potential drugs through the Cancer Therapeutic Response Portal (CTRP) and Genomics of Drug Sensitivity in Cancer (GDSC) databases that could target arginine biosynthesis genes and potentially improve the response rate to immunotherapy in patients with a high arginine biosynthesis fraction. CONCLUSION: Overall, our analyses emphasize that arginine biosynthesis genes are associated with immune evasion in several cancers. Targeting these genes may facilitate more effective immunotherapy.
-
Single nucleus multiomic atlas of human dorsal root ganglia reveals the contribution of non-neuronal cell types to pain.
Sensory neurons residing in dorsal root ganglia (DRG) transmit sensory information such as pain, itch, touch, pressure and bodily position to the central nervous system. The activity of sensory neurons is regulated by non-neuronal cell types in the DRG, including satellite glial cells (SGCs) and fibroblasts. Dysregulated gene expression in DRG cells contributes to sensory nervous system disorders such as chronic pain and itch. Understanding the genetic underpinnings of these conditions requires dissecting transcriptional regulation in human DRG (hDRG). In this study, we profiled transcriptomic and chromatin accessibility landscapes from postmortem hDRG samples at single-cell level. We demonstrate that sequencing depth significantly impacts downstream analysis, with deeper sequencing yielding more detected cells and features, improved data integration, refined clustering and annotation, and more accurate scientific interpretations. We identified nine major cell types, defined their molecular signatures, and mapped cis-regulatory landscapes. Integration of gene expression with chromatin accessibility enabled peak-gene association and transcriptional network analyses, revealing transcription factors, their target genes, and their regulatory elements. This approach uncovered cell types, genes, and cis-regulatory regions potentially driving pain conditions. Our unbiased genome-wide analysis confirmed known pain-related genes and highlighted novel candidates. These findings provide new insight into molecular mechanisms and candidate cell types involved in pain. Importantly, our results demonstrate that non-neuronal cell types, including endothelial cells, fibroblasts, macrophages, and SGCs, play critical roles in pain pathogenesis and should be investigated as therapeutic targets.
-
Reanalysis of single-cell data reveals macrophage subsets associated with the immunotherapy response and prognosis of patients with endometrial cancer.
Endometrial cancer (EC) is an aggressive gynecological malignancy with an increased incidence rate. The immune landscape crucially affects immunotherapy efficacy and prognosis in EC patients. Here, we characterized the distinct tumor microenvironment signatures of EC tumors by analyzing single-cell RNA sequencing data from Gene Expression Omnibus and bulk RNA sequencing data from The Cancer Genome Atlas, which were compared with normal endometrium. Three macrophage subsets were identified, and two of them showed tissue-specific distribution. One of the macrophage subsets was dominant in macrophages derived from EC and exhibited characteristic behaviors such as promoting tumor growth and metastasis. One of the other macrophage subsets was mainly found in normal endometrium and served functions related to antigen presentation. We also identified a macrophage subset that was found in both EC and normal endometrial tissue. However, the pathway and cellular cross-talk of this subset were completely different based on the respective origin, suggesting a tumor-related differentiation mechanism of macrophages. Additionally, the tumor-enriched macrophage subset was found to predict immunotherapy responses in EC. Notably, we selected six genes from macrophage subset markers that could predict the survival of EC patients, SCL8A1, TXN, ANXA5, CST3, CD74 and NANS, and constructed a prognostic signature. To verify the signature, we identified immunohistochemistry for the tumor samples of 83 EC patients based on the selected genes and further followed up with the survival of the patients. Our results provide strong evidence that the signature can effectively predict the prognosis of EC patients.
-
Thymosin α1 alleviates pulpitis by inhibiting ferroptosis of dental pulp cells.
Tooth pulpitis is a prevalent oral disorder. Understanding the underlying mechanisms of pulpitis and developing effective treatment strategies hold great significance. Ferroptosis has recently emerged as a new form of cell death, but the role of ferroptosis in pulpitis remains largely unknown. In our study, single-cell RNA sequencing (scRNA-seq) was used to identify cellular heterogeneity between 3 pulpitis tissue and 3 healthy pulp tissue, and explored ferroptosis occurrence in pulpitis tissue and inflamed dental pulp cells (DPCs). In scRNA-seq, 40 231 cells (Pulpitis: 17 814; Healthy pulp: 22 417) were captured, and visualized into 12 distinct cell clusters. Differentially expressed ferroptosis-related genes (DE-FRGs) were almost presented in each cluster in pulpitis vs healthy pulp. ROS and Fe2+ levels significantly rose, and immunohistochemistry showed low expression of GPX4 and high expression of PTGS2 in pulpitis. In LPS-stimulated DPCs, thymosin α1 increased the expression of GPX4 and FTL, and decreased expression of TNF-α, IL-1β, IL-6, and Fe2+ levels. In rat pulpitis models, both prothymosin α (PTMA, precursor of thymosin α1) gelatin sponge placed at the hole of pulp (LPS-P(gs)) and PTMA injection in pulp (LPS-P(i)) significantly reduced infiltration of inflammatory cells and expression of PTGS2, and increased the expression of GPX4. In RNA sequencing, the expression of DE-FRGs were reversed when thymosin α1 were added in LPS-stimulated DPCs. Collectively, single-cell atlas reveals cellular heterogeneity between pulpitis and healthy pulp, and ferroptosis occurrence in pulpitis. Thymosin α1 may reduce ferroptosis in DPCs to alleviate pulpitis and thus potentially has the ability to treat pulpitis.
-
Non-structural maintenance of chromosome condensin I complex subunit H knockdown suppresses malignant progression of esophageal squamous cell carcinoma via the Wnt/β-catenin signaling pathway.
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) remains a major cause of cancer-related mortality, and effective therapeutic targets are still limited. Non-structural maintenance of chromosome condensin I complex subunit H (NCAPH) has been implicated in tumorigenesis; however, its clinical relevance, functional roles, and underlying mechanisms in ESCC are not fully defined. We aimed to characterize the expression pattern, prognostic value, biological functions, and mechanistic basis of NCAPH in ESCC. METHODS: Public datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to evaluate NCAPH expression and clinical associations. Single-cell RNA sequencing (scRNA-seq) data were used to map cell-type-specific distribution of NCAPH in tumor and adjacent tissues. NCAPH was silenced in KYSE150 and KYSE510 cells using lentiviral short hairpin RNAs (shRNAs), followed by Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, and Transwell migration/invasion assays. A nude mouse xenograft model was established to assess the effect of NCAPH knockdown in vivo. RNA sequencing (RNA-seq), quantitative polymerase chain reaction (qPCR), western blotting, and enzyme-linked immunosorbent assay (ELISA) were performed to explore potential mechanisms. RESULTS: NCAPH was consistently upregulated in ESCC across multiple cohorts and was associated with unfavorable clinicopathological features and poorer survival. Functional assays demonstrated that NCAPH knockdown significantly inhibited ESCC cell proliferation, migration, invasion, and clonogenic growth. In vivo, NCAPH silencing suppressed xenograft tumor growth. Mechanistically, transcriptomic profiling and molecular validation indicated attenuation of Wnt/β-catenin signaling following NCAPH depletion, accompanied by reduced β-catenin and downstream targets. CONCLUSIONS: NCAPH promotes malignant progression of ESCC, at least in part through activation of the Wnt/β-catenin pathway, and may serve as a potential biomarker and therapeutic target.
-
Single-cell and machine learning-based pyroptosis-related gene signature predicts prognosis and immunotherapy response in glioblastoma.
BACKGROUND: Glioblastoma (GBM) is the most aggressive primary malignancy of the central nervous system, characterized by profound heterogeneity and an immunosuppressive microenvironment, leading to dismal prognosis. Pyroptosis, an inflammatory form of programmed cell death, has been increasingly linked to tumor immunity and progression; however, its molecular roles and clinical implications in GBM remain insufficiently understood. METHODS: We integrated bulk transcriptome profiles from TCGA-GBM, CGGA, and GEO datasets with single-cell RNA sequencing data from GSE141383 and GSE223063. A comprehensive GBM single-cell atlas was constructed using Seurat and Harmony, and malignant epithelial cells were inferred via inferCNV. Pyroptosis activity was quantified by five complementary algorithms, while Monocle2 and Slingshot were employed for pseudotime trajectory reconstruction, and SCENIC was applied for transcription factor network analysis. Candidate prognostic genes identified from malignant epithelial subsets were further used to develop a Pyroptosis-Related Gene Signature (PRGS) through a systematic evaluation of ten machine learning algorithms and their combinations, with subsequent validation across multiple cohorts. Functional enrichment (GSVA, GSEA), tumor microenvironment estimation (ESTIMATE, ssGSEA), drug sensitivity prediction (GDSC2), and in vitro experiments were performed to characterize the biological and therapeutic relevance of PRGS, with MAP1B selected for experimental validation. RESULTS: Single-cell analyses revealed heterogeneous pyroptosis activity across GBM cell populations. Distinct ligand-receptor communications were observed between high- and low-pyroptosis groups, among which the SPP1-centered signaling axis showed pronounced remodeling, suggesting a pivotal role in tumor-immune crosstalk. Pseudotime and regulatory network analyses of malignant epithelial cells further delineated differentiation trajectories and transcriptional regulators. The PRGS, established by StepCox[both]+Ridge modeling, demonstrated robust prognostic stratification and predictive power across independent datasets. High PRGS scores were consistently associated with poorer survival outcomes, higher TIDE scores, and reduced IPS values, indicating enhanced immune evasion and attenuated immunotherapy benefit. Enrichment analyses highlighted that high PRGS tumors were linked to metabolic reprogramming and DNA repair pathways, whereas low PRGS tumors exhibited signatures of immune activation. Drug sensitivity analyses revealed distinct therapeutic vulnerabilities between subgroups. Functional assays confirmed that MAP1B promotes proliferation, migration, and invasion in GBM cells, reinforcing its oncogenic role. CONCLUSION: This study systematically elucidates the role of pyroptosis in GBM and establishes PRGS as a reliable prognostic biomarker. PRGS not only refines risk stratification and predicts immunotherapy response but also provides molecular insights into tumor metabolism and immune regulation, thereby offering potential avenues for targeted therapeutic strategies in GBM.
-
Integrated Bioinformatics Analysis Identifies NCAPG2 as an Immune-Related Prognostic Biomarker in Breast Cancer.
BACKGROUND: Non-SMC condensin II complex subunit G2 (NCAPG2) is an important molecule in regulating chromosome segregation of mitosis and acts as an oncogene and biomarker in various tumors. This study aimed to explore the role of NCAPG2 in breast cancer (BC). METHODS: The mRNA and protein expression of NCAPG2 was explored in the Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), and bc-GenExMiner databases. Survival analyses were performed using the Kaplan-Meier plotter and bc-GenExMiner databases. We used the COSMIC, CistromeDB, and cBioPortal databases to analyze the transcriptional regulation and genetic alteration. Function enrichment analyses were performed with CancerSEA and Metascape database. RESULTS: NCAPG2 expression was significantly higher in BC than normal samples. NCAPG2 expression was positively correlated with the Scarff-Bloom-Richardson (SBR) grade, HER2 status, lymph nodal status, TP53 and BRCA1/2 mutation, and Nottingham prognostic index (NPI), while negatively correlated with age, ER status, and PR status. Survival analyses indicated that overexpressed NCAPG2 was associated with the adverse prognosis of BC. Gene Set Enrichment Analysis (GSEA) and function enrichment analyses of single-cell and co-expressed genes of NCAPG2 consistently showed that NCAPG2 was involved in cell cycle, immune, DNA damage, cancer-related pathways, proliferation, and DNA repair. The result of TIMER showed that NCAPG2 was associated with infiltrating immune cells and the exhausted T cell phenotype, such as CD8+ T cells, PD-1, CTLA4, and TIM-3. CONCLUSION: We found that the mRNA and protein expression of NCAPG2 was upregulated in BC. Overexpressed NCAPG2 might act as an adverse prognosis biomarker in BRCA and had a distinct function in the cell cycle, proliferation, and immune infiltration.