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: 4 882
Страница 38 из 489-
Single-cell landscape of goose thymus uncovers developmental and regulatory dynamics of T cell differentiation.
The thymus is vital for T cell development, yet avian thymocyte maturation remains poorly characterized. Here, we present a single-cell transcriptomic atlas of thymic development in Zhedong White geese across embryonic, gosling, juvenile, and adult stages. Morphological and histological analysis revealed a multilobulated, paired thymus with rapid post-hatch expansion and age-dependent involution. Single-cell RNA sequencing identified all major thymic cell types, with T cells predominant and γδ T cells unusually abundant compared to mammals. High-resolution profiling defined key T cell subsets and reconstructed sequential differentiation, showing DN cells transition from pre-commitment states marked by BCL11A, SPI1, and HHEX to committed states (BCL11B, TCF7) and β-selection gene activation. Thymic epithelial cells functioned as central signaling hubs, mediating microenvironmental regulation. Comparative analysis with human and mouse thymus revealed a conserved developmental framework, yet pronounced species-specific differences at the DP stage and in γδ T cell enrichment. These findings contribute foundational insights for avian immunology and poultry breeding.
-
A developmental single-cell atlas of the Drosophila visual system glia reveals cell type diversification and subcellular mRNA compartmentalization.
Glial cells are essential for proper nervous system development and function. To understand glial development and function, we comprehensively annotated the glial cells from two large single-cell mRNA-sequencing (scRNA-seq) atlases of the developing Drosophila visual system. This allowed us to identify all glial cell types from larval to adult stages and follow their developmental trajectories to understand how the diversity of glial types is generated during development. We show that whereas most glial types, such as chiasm glia, gradually change their transcriptome as they mature during development, neuropil glia that transcriptionally appear as a single-cell class in larvae, splits into ensheathing (EG) and astrocyte-like (ALG) glia types during pupal stages. We have experimentally validated these developmental trajectories and identified the genetic markers expressed through the differentiation between EG and ALG classes. Unexpectedly, our analysis of scRNA-seq datasets allowed us to discover that the transcriptome of glial cell bodies can be distinguished from that of their processes. We have identified that processes are enriched for distinct mRNAs that were validated in vivo. This work provides the most detailed transcriptomic analysis of optic lobe glia during development and helps explain the expansion of glial diversity observed in the adult visual system. We also present an innovative computational approach to identify mRNA species that are differentially localized to cell bodies or cellular processes.
-
Single-cell sequencing and network pharmacology coupled with molecular docking and experimental validation reveal the effects of YPFS on macrophages in stage I non-small cell lung cancer.
BACKGROUND: Non-small cell lung cancer (NSCLC), the most common subtype of lung cancer, presents major clinical challenges owing to its highly complex tumor microenvironment and substantial cellular heterogeneity. A comprehensive understanding of the immune landscape-particularly the phenotypic diversity and functional roles of macrophage subpopulations-is critical for identifying novel therapeutic targets and developing more effective treatment strategies. METHODS: We constructed a comprehensive single-cell atlas of Stage I NSCLC using single-cell RNA sequencing (scRNA-seq) to characterize immune heterogeneity, with particular emphasis on macrophage subsets. Network pharmacology was employed to investigate the interactions between AHSA1 and bioactive compounds derived from the traditional Chinese medicine formulation Yu Ping Feng San (YPFS). To further evaluate these interactions, molecular docking simulations were performed to assess binding affinities and elucidate the potential regulatory effects on macrophage polarization. RESULTS: ScRNA-seq analysis revealed heterogeneous macrophage subtypes, each exhibiting distinct roles in tumor progression. AHSA1 was identified as a key regulator of macrophage polarization, with higher expression levels associated with unfavorable prognosis. Through network pharmacology and molecular docking, strong binding affinities were observed between AHSA1 and Yu Ping Feng San (YPFS)-derived compounds, including wogonin, kaempferol, and quercetin. Notably, quercetin displayed the highest binding affinity and exerted the strongest inhibitory effect on M2 macrophage polarization. CONCLUSION: These findings identify AHSA1 as a pivotal regulator of macrophage polarization in NSCLC and position quercetin as a promising macrophage-targeted therapeutic candidate. Furthermore, the results highlight the potential of Yu Ping Feng San (YPFS) as a complementary therapeutic strategy for NSCLC, offering a bridge between traditional Chinese medicine and modern oncology.
-
Subgroup-Specific Associations of GRIA Genes Encoding AMPA Glutamate Receptor Subunits with Patient Survival in Medulloblastoma.
Brain cancers hijack biological systems involved in neural development and synaptic plasticity. Medulloblastoma (MB), the most common malignant brain tumor in children, is thought to arise from disruptions in neurodevelopmental programs. Glutamatergic transmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) has been implicated in synaptic communication between adult brain tumors and surrounding neurons; however, the possible role of AMPARs in MB remains largely unexplored. Here, we analyzed the expression of genes encoding AMPAR subunits, GRIA1-4, in datasets of MB tumors and cell lines, revealing distinct expression patterns and associations with overall survival (OS) across molecular subgroups and histological variants. Expression levels differed among MB molecular subgroups. Analysis using single-cell RNA sequencing (scRNA-seq) was consistent with enrichment of GRIA1 in Group 3 and GRIA4 in sonic hedgehog (SHH) MB. Higher GRIA1, GRIA2, and GRIA4 transcription was associated with more favorable patient outcomes in specific MB subgroups. In contrast, high expression of GRIA3 in SHH, or of either GRIA3 or GRIA4 in Group 3 MB, was associated with worse prognosis. Particularly robust but opposing associations with patient survival were found for GRIA3 and GRIA4 in SHH MB. Analysis of GRIA mRNA levels in MB cell lines using both quantitative reverse transcription polymerase chain reaction (qRT-PCR) and data from The Human Protein Atlas, supported some of the gene expression patterns observed in tumors. Together, these findings suggest that GRIA genes and their corresponding AMPAR subunits may have subgroup-specific prognostic relevance in MB.
-
Comparative single-nucleus transcriptomics reveals asymmetric evolution of the Drosophila male and female germlines.
Reproductive organs vary widely across species yet share conserved cell types that produce gametes, sustaining species' perpetuation. However, tissue-level comparisons mask critical differences among cell types, obscuring where evolutionary divergence occurs even between closely related species. We quantified expression divergence at cell-type resolution between two sibling species, Drosophila melanogaster and D. simulans, while disentangling adaptive and nonadaptive evolutionary mechanisms. We built a comparative single-nucleus transcriptomic atlas of over 100,000 nuclei from testes and ovaries of both species. Our analysis revealed sharply heterogeneous divergence across testis cell types, contrasting with a broader conservation across ovary cell types. Notably, in both organs, ~40% of genes showing interspecific differences did so in only one cell type. In the testis, spermatogonia were largely conserved, whereas divergence peaked in primary spermatocytes with extensive rewiring of coexpression modules linked to microtubule and mitochondrial functions. In the ovary, expression was largely conserved, except in early germline and late follicle cells, which showed shifts in oogenesis and cell-cycle-related coexpression modules. Divergent cell types in both tissues were enriched for evolutionarily young genes with narrow expression breadth and faster protein evolution rates. Additionally, the ovary exhibited a faster-X effect consistent with adaptive evolution. These findings reveal a fundamental asymmetry in how male and female germlines evolve, with functional constraints relaxed in specific testis cell types but broadly maintained across the ovary. Our work provides an evolutionary framework explaining how core reproductive functions are safeguarded during species diversification while identifying germline cells that drive evolutionary change.
-
Quantifying pathological progression from single-cell transcriptomic data with scPSS.
The surge in single-cell data sets and reference atlases has enabled the comparison of cell states across conditions, yet a gap persists in quantifying pathological shifts from healthy cell states. To address this gap, we introduce single-cell Pathological Shift Scoring (scPSS), which provides a statistical measure for how much a "query" cell from a diseased sample has shifted away from a reference group of healthy cells. In scPSS, the distance of a cell to its k-th nearest reference cell is considered as its pathological shift score. Euclidean distances in the top n principal component space of the gene expressions are used to measure distances between cells. The distribution of shift scores of the reference cells forms a null model. This allows a P-value to be assigned to each query cell's shift score, quantifying its statistical significance of being in the reference cell group. This makes our method both simple and statistically rigorous. The key strength of scPSS is its applicability in a "semisupervised" setting, where only healthy reference cells are known and diseased-labeled data are not provided for model training. As existing methods do not support cell-level pathological progression measurement in this setting, we adapt state-of-the-art supervised pathological prediction and contrastive models for benchmarking. Comparative evaluations against these adapted models demonstrate our method's superiority in accuracy and efficiency. Additionally, we show that the aggregation of cell-level pathological scores from scPSS can be used to predict health conditions at the individual level.
-
Establishment of an ovarian cancer exhausted CD8+T cells-related genes model by integrated analysis of scRNA-seq and bulk RNA-seq.
Ovarian cancer (OC) was the fifth leading cause of cancer death and the deadliest gynecological cancer in women. This was largely attributed to its late diagnosis, high therapeutic resistance, and a dearth of effective treatments. Clinical and preclinical studies have revealed that tumor-infiltrating CD8+T cells often lost their effector function, the dysfunctional state of CD8+T cells was known as exhaustion. Our objective was to identify genes associated with exhausted CD8+T cells (CD8TEXGs) and their prognostic significance in OC. We downloaded the RNA-seq and clinical data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. CD8TEXGs were initially identified from single-cell RNA-seq (scRNA-seq) datasets, then univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression were utilized to calculate risk score and to develop the CD8TEXGs risk signature. Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, and calibration were conducted to verify and evaluate the risk signature. Gene set enrichment analyses (GSEA) in the risk groups were used to figure out the closely correlated pathways with the risk group. The role of risk score has been further explored in the homologous recombination repair deficiency (HRD), BRAC1/2 gene mutations and tumor mutation burden (TMB). A risk signature with 4 CD8TEXGs in OC was finally built in the TCGA database and further validated in large GEO cohorts. The signature also demonstrated broad applicability across various types of cancer in the pan-cancer analysis. The high-risk score was significantly associated with a worse prognosis and the risk score was proven to be an independent prognostic biomarker. The 1-, 3-, and 5-years ROC values, nomogram, calibration, and comparison with the previously published models confirmed the excellent prediction power of this model. The low-risk group patients tended to exhibit a higher HRD score, BRCA1/2 gene mutation ratio and TMB. The low-risk group patients were more sensitive to Poly-ADP-ribose polymerase inhibitors (PARPi). Our findings of the prognostic value of CD8TEXGs in prognosis and drug response provided valuable insights into the molecular mechanisms and clinical management of OC.
-
From Normal Mucosa to Colorectal Cancer in Lynch Syndrome: Single-Cell Dissection of Cellular Heterogeneity and Communication Networks.
OBJECTIVE: To generate a single-cell atlas of colorectal cancer (CRC) development in Lynch syndrome (LS), and to delineate the associated cellular reprogramming and intercellular communication networks. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on matched normal mucosa, adenoma, and carcinoma tissues obtained from patients with LS. Following quality control and batch-effect correction, we used the Uniform Manifold Approximation and Projection (UMAP) clustering and marker gene analyses to annotate cell types, differential expression analyses to identify stage-specific genes, and GSVA analyses to assess pathway activity. Functional assays with patient-derived organoids and transwell experiments were employed to validate the role of DMBT1. Cell-cell communication networks were inferred using Cell Chat. RESULTS: We identified twelve distinct cell clusters and observed marked shifts in cellular composition during CRC progression, including increased T lymphocytes and macrophages and decreased epithelial cells. Trajectory analyses suggested a potential differentiation path from BEST4+ to CEMIP+/EGFR+ epithelial cells. DMBT1 was consistently down-regulated and its depletion activated the WNT/β-catenin pathway, enhancing organoid growth and cell migration. Expansion of CCR8+ regulatory T cells and C1QC+/IDO1+/IL1B+ macrophages indicated an immunosuppressive and pro-tumorigenic microenvironment. CONCLUSIONS: This study provides a comprehensive single-cell resource for LS-associated CRC and highlights DMBT1 loss, epithelial remodelling, and immune dysregulation as potential therapeutic targets.
-
Single-cell transcriptomics identifies a candidate osmoregulatory cell population in the mid-intestine of the saline-alkaline fish Gymnocypris przewalskii.
Saline-alkaline fishes maintain internal homeostasis through effective intestinal ion and acid-base regulation. However, the specific intestinal epithelial cell populations mediating these functions remain poorly characterized. Here, we performed single-cell RNA sequencing on 23,909 mid-intestinal cells from juvenile Gymnocypris przewalskii, a fish native to the saline-alkaline Lake Qinghai, to generate a cell atlas of the mid-intestine. Several major cell classes were identified, including epithelial cells (ECs), enteroendocrine cells (EECs), goblet cells (GCs), and leukocytes (LCs), each exhibiting distinct subpopulation heterogeneity. Within the epithelial cell lineage, we identified a distinct cluster characterized by high expression of best4, cftr, and ca2, suggesting a candidate osmoregulatory cell population (referred to as Best4+ cells). To further evaluate this marker set, we compared fish exposed to freshwater with those exposed to artificial lake water and observed significantly elevated gene expression levels of best4, cftr and ca2 in intestinal cells under lake water conditions. Immunofluorescence detection of BEST4 and CA2 in mid-intestinal sections further provided tissue-level support for the epithelial association of these candidate markers. In addition to this candidate osmoregulatory cell population, the atlas also resolved absorptive epithelial cell states, together with heterogeneity within enteroendocrine cell, goblet cell, and leukocyte lineages. Overall, these findings identify a candidate epithelial cell population relevant to intestinal ion and acid-base regulation in G. przewalskii and clarify the cellular basis of intestinal specialization under saline-alkaline stress.
-
Consensus Pituitary Atlas, a scalable resource for annotation, novel marker discovery, and analyses in mouse pituitary gland research.
Previous single-cell profiling studies of the pituitary gland have yielded minimally reproducible insights due to their low statistical power and methodological inconsistencies. To address this, we generate the uniformly pre-processed Consensus Pituitary Atlas (CPA) using all 283 existing mouse pituitary single-cell datasets (∼1.3 million high-quality cells). The CPA reveals cell typing and lineage markers, including low-expression transcripts that previous analyses could not detect. Leveraging the scale of the CPA, we develop machine learning models to automate and standardize cell type annotation and doublet identification for future studies. Utilizing the curated metadata, we identify sex-biased and age-dependent gene expression patterns at cell type resolution. To uncover drivers of cell fates, first we determine consensus cell communication patterns. Second, we use RNA sequencing and chromatin accessibility data to identify transcription factors associated with cell fates across modalities. The epitome platform provides a user-friendly interface with the CPA and allows streamlined analyses.