Браузер не даёт сохранять данные (например, приватный режим): закладки пропадут после закрытия вкладки.
Поиск статей PubMed
Ключевые слова, автор, журнал, годы — результаты из PubMed, аннотации с переводом на русский, закладки в браузере.
Найдено: 4 928
Страница 246 из 493-
The Inflammatory Characteristics of Symptomatic Glioma Associated With Poor Prognosis and Chemoresistance via Tumor Necrosis Factor Signaling Pathway.
BACKGROUND: Among gliomas, the most common primary malignant brain tumor, incidental gliomas account for 2.5%-5% of cases. The controversy over whether to pursue immediate treatment or adopt a wait-and-see approach remains, and more molecular and immunological evidence is needed for definitive treatment decisions. METHODS: Total RNA sequencing (RNA-seq) data and single cell RNA sequencing (scRNA-seq) data were retrospectively analyzed to compare the molecular and immunological tumor microenvironment differences between incidental glioma and symptomatic glioma samples. These were classified using symptom data from The Cancer Genome Atlas (TCGA) and public dataset. RESULTS: RNA-seq analysis of the GBMLGG dataset identified 343 genes upregulated in symptomatic glioma and 118 in incidental glioma, with 104 common genes upregulated in symptomatic glioma across both the TCGA and Chinese Glioma Genome Atlas (CGGA) datasets. Enrichment analysis revealed that these 104 genes in symptomatic glioma were significantly associated with immunological pathways. scRNA-seq analysis of glioma revealed 11 cell types, including T cells, myeloid cells, and oligodendrocytes, with the tumor necrosis factor (TNF) signaling pathway strongly influencing other cell types, particularly myeloid cells. Enrichment and survival analyses showed that TNF signaling is associated with temozolomide resistance and poorer prognosis in glioma patients. CONCLUSION: The findings suggest that symptomatic glioma enhances inflammatory responses linked to poor prognosis and chemoresistance. This supports the hypothesis that immediate treatment of incidental glioma may improve patient outcomes over a wait-and-see approach.
-
Single-cell analysis of the epigenome and 3D chromatin architecture in the human retina.
Most genetic risk variants linked to ocular diseases are non-protein coding and presumably contribute to disease through dysregulation of gene expression, however, deeper understanding of their mechanisms of action has been impeded by an incomplete annotation of the transcriptional regulatory elements across different retinal cell types. To address this knowledge gap, we carried out single-cell multiomics assays to investigate gene expression, chromatin accessibility, DNA methylome and 3D chromatin architecture in human retina, macula, and retinal pigment epithelium (RPE)/choroid. We identified 420,824 unique candidate regulatory elements and characterized their chromatin states in 23 sub-classes of retinal cells. Comparative analysis of chromatin landscapes between human and mouse retina cells further revealed both evolutionarily conserved and divergent retinal gene-regulatory programs. Leveraging the rapid advancements in deep-learning techniques, we developed sequence-based predictors to interpret non-coding risk variants of retina diseases. Our study establishes retina-wide, single-cell transcriptome, epigenome, and 3D genome atlases, and provides a resource for studying the gene regulatory programs of the human retina and relevant diseases.
-
Single-Cell RNA Sequencing Reveals Atlas of Yak Testis Cells.
Spermatogenesis is a complex process that involves proliferation and differentiation of diploid male germ cells into haploid flagellated sperm and requires intricate interactions between testicular somatic cells and germ cells. The cellular heterogeneity of this process presents a challenge in analyzing the different cell types at various developmental stages. Single-cell RNA sequencing (scRNA-seq) provides a useful tool for exploring cellular heterogeneity. In this study, we performed a comprehensive and unbiased single-cell transcriptomic study of spermatogenesis in sexually mature 4-year-old yak using 10× Genomics scRNA-seq. Our scRNA-seq analysis identified six somatic cell types and various germ cells, including spermatogonial stem cells, spermatogonia, early-spermatocytes, late-spermatocytes, and spermatids in yak testis. Pseudo-timing analysis showed that Leydig and myoid cells originated from common progenitor cells in yaks. Moreover, functional enrichment analysis demonstrated that the top expressed genes in yak testicular somatic cells were significantly enriched in the cAMP signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and ECM receptor interactions. Throughout the spermatogenesis process, genes related to spermatogenesis, cell differentiation, DNA binding, and ATP binding were expressed. Using immunohistochemical techniques, we identified candidate marker genes for spermatogonial stem cells and Sertoli cells. Our research provides new insights into yak spermatogenesis and the development of various types of cells in the testis, and presents more reliable marker proteins for in vitro culture and identification of yak spermatogonial stem cells in the later stage.
-
Gene expression variation in Arabidopsis embryos at single-nucleus resolution.
Soon after fertilization of egg and sperm, plant genomes become transcriptionally activated and drive a series of coordinated cell divisions to form the basic body plan during embryogenesis. Early embryonic cells rapidly diversify from each other, and investigation of the corresponding gene expression dynamics can help elucidate underlying cellular differentiation programs. However, current plant embryonic transcriptome datasets either lack cell-specific information or have RNA contamination from surrounding non-embryonic tissues. We have coupled fluorescence-activated nuclei sorting together with single-nucleus mRNA-sequencing to construct a gene expression atlas of Arabidopsis thaliana early embryos at single-cell resolution. In addition to characterizing cell-specific transcriptomes, we found evidence that distinct epigenetic and transcriptional regulatory mechanisms operate across emerging embryonic cell types. These datasets and analyses, as well as the approach we devised, are expected to facilitate the discovery of molecular mechanisms underlying pattern formation in plant embryos. This article has an associated 'The people behind the papers' interview.
-
Comprehensive analysis of mitochondria-associated genes in glioblastoma via single-cell and bulk RNA sequencing.
Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options and poor survival. Mitochondrial dysfunction and metabolic reprogramming, particularly the Warburg effect, are increasingly recognized as critical drivers of GBM progression. Here, we integrated single-cell (scRNA-seq) and bulk RNA-sequencing (bulk RNA-seq) data to comprehensively examine mitochondria-associated genes in GBM. We identified differentially expressed mitochondrial genes with prognostic significance and constructed a 9-gene risk signature—ACOT7, THEM5, MTHFD2, ABCB7, PICK1, PDK3, ARMCX6, GSTK1, and SSBP1—using LASSO and Cox regression. This signature robustly stratified patients into high- and low-risk groups in both The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) cohorts, remaining an independent prognostic factor in multivariate analyses. Time-dependent ROC AUCs were 0.729, 0.813, and 0.828 at 1, 2, and 3 years in TCGA, and 0.597, 0.650, and 0.546 in CGGA. A nomogram integrating the signature with clinical variables achieved AUCs of 0.649, 0.820, and 0.854 at 1, 3, and 5 years, with good 1/2/3-year calibration. Functional enrichment and clustering analyses revealed distinct metabolic phenotypes and survival differences between subtypes. Single-cell pseudotime analysis showed a transition from oxidative phosphorylation to glycolysis in malignant cells, aligning with the Warburg effect and implicating metabolic reprogramming in immune modulation. Our findings underscore the prognostic value of mitochondria-associated genes and suggest potential therapeutic targets for disrupting GBM metabolism. Overall, these results establish a mitochondria-centric prognostic model supported by single-cell context; findings are hypothesis-generating and warrant prospective and experimental validation.
-
The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing.
A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Here, we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients, and drew a systematic immune cell transcriptome atlas. Joint analyses of the distinct cellular compositions, differentially expressed genes (DEGs), cell-cell interactions, pseudotime trajectory, transcriptomic factors and prognostic factors based on The Cancer Genome Atlas (TCGA), revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages (Mφ) subtypes in the immune microenvironment heterogeneity between LUAD and LUSC. The dominant subtype of Mφ was FABP4-Mφ in LUAD and SPP1-Mφ in LUSC. Importantly, we identified a novel lymphocyte-related Mφ cluster, which we named SELENOP-Mφ, and further established its antitumor role in both types, especially in LUAD. Our comprehensive depiction of the immune heterogeneity and definition of Mφ clusters could help design personalized treatment for lung cancer patients in clinical practice.
-
Single-cell RNA-sequencing atlas reveals an FABP1-dependent immunosuppressive environment in hepatocellular carcinoma.
BACKGROUND: Single-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply understanding cell behavior in a complicated tumor microenvironment. Although several previous studies have examined scRNA-seq for hepatocellular carcinoma (HCC) tissues, no one has tested and analyzed HCC with different stages. METHODS: In this investigation, immune cells isolated from surrounding normal tissues and cancer tissues from 3 II-stage and 4 III-stage HCC cases were subjected to deep scRNA-seq. The analysis included 15 samples. We distinguished developmentally relevant trajectories, unique immune cell subtypes, and enriched pathways regarding differential genes. Western blot and co-immunoprecipitation were performed to demonstrate the interaction between fatty acid binding protein 1 (FABP1) and peroxisome proliferator-activated receptor gamma(PPARG). In vivo experiments were performed in a C57BL/6 mouse model of HCC established via subcutaneous injection. RESULTS: FABP1 was discovered to be overexpressed in tumor-associated macrophages (TAMs) with III-stage HCC tissues compared with II-stage HCC tissues. This finding was fully supported by immunofluorescence detection in significant amounts of HCC human samples. FABP1 deficiency in TAMs inhibited HCC progression in vitro. Mechanistically, FABP1 interacted with PPARG/CD36 in TAMs to increase fatty acid oxidation in HCC. When compared with C57BL/6 mice of the wild type, tumors in FABP1-/- mice consistently showed attenuation. The FABP1-/- group's relative proportion of regulatory T cells and natural killer cells showed a downward trend, while dendritic cells, M1 macrophages, and B cells showed an upward trend, according to the results of mass cytometry. In further clinical translation, we found that orlistat significantly inhibited FABP1 activity, while the combination of anti-programmed cell death 1(PD-1) could synergistically treat HCC progression. Liposomes loaded with orlistat and connected with IR780 probe could further enhance the therapeutic effect of orlistat and visualize drug metabolism in vivo. CONCLUSIONS: ScRNA-seq atlas revealed an FABP1-dependent immunosuppressive environment in HCC. Orlistat significantly inhibited FABP1 activity, while the combination of anti-PD-1 could synergistically treat HCC progression. This study identified new treatment targets and strategies for HCC progression, contributing to patients with advanced HCC from new perspectives.
-
Integrated single-cell and bulk RNA sequencing reveals prognostic and immunotherapy-associated myofibroblastic cancer-associated fibroblast subtypes in head and neck squamous cell carcinoma.
BACKGROUND: Cancer-associated fibroblasts (CAFs) are involved in some critical aspects of the pathogenesis of head and neck squamous cell carcinoma (HNSCC), including the formation of a tumor-permissive extracellular matrix (ECM) structure, angiogenesis, and the immune and metabolic reprogramming of the tumor microenvironment (TME). This study aimed to examine the plasticity and metabolic heterogeneity of CAFs in HNSCC patients before and after immunotherapy. METHODS: An integrated single-cell and bulk RNA sequencing (RNA-seq) analysis based on data from the GSE195832, GSE65868, and The Cancer Genome Atlas (TCGA)-HNSCC datasets was conducted. The functional plasticity and transcriptome diversity of the categorized CAF subtypes were analyzed using the DoRothEA tool and scMetabolism package. The relationship between the genes specifically expressed in the myofibroblast-like cancer-associated fibroblast (myCAF) subtype and prognosis was then examined by univariate and multivariate analyses. The influence of myCAF on immune cell modulation within the TME was analyzed using the Seurat and clusterProfiler packages. The therapeutic strategies for HNSCC were explored using the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing datasets. RESULTS: In total, seven types of cells were annotated based on 11 clusters. The CAFs were then re-categorized into the following three subtypes: inflammatory cancer-associated fibroblasts (iCAFs), proliferating cancer-associated fibroblasts (pCAFs), and myCAFs. The percentage of myCAFs was reduced in HNSCC following the immunotherapy. The functional plasticity of the CAFs was further confirmed by the diverse enriched pathways. Notably, the myCAFs were closely associated with DNA repair, oxidative phosphorylation, and transcription factor E2F targets. Further, the myCAFs were found to be the subtype most relevant to the prognosis of HNSCC and were found to be involved in modulating the immune cells in the TME of HNSCC. Additionally, a higher myCAF score was related to the higher half-maximal inhibitory concentration (IC50) values of D-4476, GW-583340, spautin-1, and VER-155008, and the lower IC50 values of JTE-607, TG100-115, ML320, and TGX-221. Moreover, patients with lower myCAF scores responded better to immunotherapy. CONCLUSIONS: This study, which was based on single-cell and bulk RNA-seq analyses, showed the plasticity and metabolic heterogeneity of CAFs in HNSCC. Our findings may contribute to understandings of the immunotherapy response in HNSCC.
-
The neurotoxicity of Chlorantraniliprole to Helicoverpa armigera larvae.
Chlorantraniliprole (CAP) is a mainstream diamide insecticide widely used against lepidopteran pests such as Helicoverpa armigera. Given that most insecticides act via neurotoxic mechanisms, we reasoned that CAP, despite its well-established action on ryanodine receptors (RyRs), may also disrupt nervous system function through additional targets. Insect neurotoxicity is a coordinated process involving neurons and glial cells: voltage-gated sodium (Nav) and potassium (Kv) channels are common insecticide targets, however, their involvement in CAP-induced neurotoxicity has not been established, and glial contributions are poorly understood. We elucidated CAP's multi-target mechanisms by constructing the first single-cell transcriptomic atlas of the H. armigera ventral nerve cord (VNC) using scRNA-seq, validated by whole-cell patch-clamp electrophysiology and RT-qPCR. Results showed that CAP modulated the kinetics of Nav channel in a concentration-dependent manner and suppressed Kv channel currents, confirming both as novel non-canonical targets. scRNA-seq identified VNC cell types, identifying NKCC (perineurial glia-enriched) and UGT39B1 (subperineurial glia-enriched); both were upregulated after 24 h LC30 CAP exposure. These results indicate that CAP modulates Nav and Kv channels at relatively high concentrations. As potential functional targets, these channels supplement the primary RyR-mediated action of CAP, and imply a partial mechanistic similarity to pyrethroids via regulation of Nav channels. Moreover, the VNC atlas facilitated the identification of glial-specific markers (NKCC and UGT39B1), clarifying glial involvement. Collectively, our work advances multi-target understanding of diamide insecticides, provides candidate synergists, and supports "neuron-glial dual-target" strategies for managing H. armigera resistance.
-
Multimodal evidence for bone lymphatics in skeletal health and repair.
Previous studies predominantly associated lymphatics with skeletal disease and bone loss. However, building on our work, bone lymphatics are emerging as a paradigm-shifting component of the skeletal microenvironment, illustrating their role as positive regulators of bone mass and repair. Here, we present a comprehensive analysis integrating spatial transcriptomics, single-cell RNA sequencing, and imaging across murine and human bones. Spatial transcriptomics identifies Prox1+ endothelial cells embedded within bone. Reanalysis of multiple scRNA-seq datasets confirms Prox1+ lymphatic endothelial cells (LECs) in bones, despite their underrepresentation in soft-tissue endothelial cell atlases. Periosteum is an insufficient source for bone lymphatics because it contains only sparse LECs. Our analyses further demonstrate that certain mouse models lack the sensitivity required to detect bone lymphatics and highlight the importance of high-resolution imaging. Collectively, convergent multimodal evidence substantiates LECs as an integral functional component of the skeletal microenvironment. This Matters Arising Response paper addresses the Meng et al. (2026) Matters Arising paper, published concurrently in this issue.