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 219 из 493-
A cDC1-NK/T-Malignant Cell Circuit Drives Immunogenic Remodeling Under PD-1 Blockade in Gastric Cancer.
The gastric cancer (GC) tumor microenvironment (TME) constitutes a complex and dynamic ecosystem in which immune, stromal, and malignant cells (MCs) collectively shape therapeutic responses. The dynamics of GC TME remodeling in different treatment contexts remain unclear. We performed single-cell RNA sequencing (scRNA-seq) of GC biopsy specimens from treatment-naïve patients (TN) and patients treated with chemotherapy (C), chemotherapy plus nivolumab (CN), or chemotherapy plus trastuzumab (CT), and found that CN treatment enhanced natural killer (NK)/T cell-associated immunogenicity in GC TMEs. In CN TMEs, MCs upregulate MHC-I- and inflammation-related genes. Conventional type 1 dendritic cells (cDC1), one subcluster of dendritic cells (DCs), concurrently exhibited activation of antigen-presentation and T cell-stimulatory programs, indicating intensified communication between NK/CD8+ T cells and cDC1 in the CN TMEs. The cell-cell interaction analyses uncovered an intensified X-C Motif Chemokine Ligand 1 (XCL1) - X-C motif chemokine receptor 1 (XCR1) chemotactic axis linking NK/CD8+ T cells and cDC1, highlighting the formation of "the MCs-cDC1-NK/CD8+ T cells circuit" to reinforce antitumor immunity in the CN TMEs. Furthermore, a reduced cytotoxic NK sub-cluster, which showed high XCL1 expression, was enriched among CN responders, and its transcriptional signature was significantly correlated with favorable survival in the Cancer Genome Atlas GC cohort. Our findings delineate an immunostimulatory circuit driven by NK/CD8+ T-DCs-MCs interactions to orchestrate the immune cycle under CN therapy in GC TMEs.
-
Single-cell RNA sequencing reveals a cellular atlas of the sheep testis.
Spermatogenesis is a highly regulated biological process involving various cell types, making the accurate identification and classification of different cell populations challenging. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for resolving cellular heterogeneity at high resolution. In this study, 10× Genomics Chromium™ scRNA-seq was employed to analyze 15,826 testicular cells from three 6-month-old sexually mature Hu sheep, and a high-resolution single-cell transcriptomic atlas was generated. Specifically, six somatic cell subtypes and five germ cell subtypes were identified, which revealed the differentiation trajectory of spermatogenesis. Notably, pseudo-time analysis suggested that Leydig cells and peritubular myoid cells may originate from a common progenitor lineage in sheep. Highly expressed genes were enriched in pathways such as cAMP signaling, PI3K-Akt, and ECM-receptor interaction. Furthermore, immunohistochemical analysis validated specific marker proteins for certain cell types. Collectively, these findings provide novel insights into spermatogenesis and serve as a valuable reference for the in vitro culture of male germ cells.
-
PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data.
Single-cell RNA sequencing is an increasingly used method to measure gene expression at the single cell level and build cell-type atlases of tissues. Hundreds of single-cell sequencing datasets have already been published. However, studies are frequently deposited as raw data, a format difficult to access for biological researchers due to the need for data processing using complex computational pipelines. We have implemented an online database, PanglaoDB, accessible through a user-friendly interface that can be used to explore published mouse and human single cell RNA sequencing studies. PanglaoDB contains pre-processed and pre-computed analyses from more than 1054 single-cell experiments covering most major single cell platforms and protocols, based on more than 4 million cells from a wide range of tissues and organs. The online interface allows users to query and explore cell types, genetic pathways and regulatory networks. In addition, we have established a community-curated cell-type marker compendium, containing more than 6000 gene-cell-type associations, as a resource for automatic annotation of cell types.
-
Unraveling Traditional Chinese Medicine with single-cell RNA sequencing: Current applications and future frontiers.
BACKGROUND: Single-cell RNA sequencing (scRNA-seq) has emerged as a transformative tool in biomedical research, overcoming the limitations of bulk RNA sequencing by resolving cellular heterogeneity, identifying rare cell subtypes, and reconstructing dynamic regulatory networks. This technology holds unprecedented potential for advancing Traditional Chinese Medicine (TCM) research, which faces challenges in deciphering the multi-component, multi-target mechanisms and heterogeneous syndromes using conventional methods. METHODS: Relevant studies were retrieved from PubMed, Web of Science, Google Scholar, and CNKI up to June 2025. Search keywords included "single-cell RNA sequencing", "Traditional Chinese Medicine", "tumor", "inflammatory and autoimmune", and "cardiovascular, cerebrovascular". The inclusion criteria were as follows: (a) original research articles; (b) the application of scRNA-seq in TCM-related research, mainly for TCM in research related to tumors, inflammatory and autoimmune diseases, cardiovascular and cerebrovascular diseases, safety evaluation of TCM, and TCM Syndrome Research. The exclusion criteria comprised: (a) studies irrelevant to the review topic; (b) studies that utilized public datasets solely for data mining. RESULTS: scRNA-seq enables precise identification of bioactive targets of herbal compounds, dissection of synergistic modulation of cellular networks by TCM formulas, and construction of syndrome-associated molecular atlases. Its applications span diverse fields: unraveling immune regulation mechanisms of TCM in tumor therapy, elucidating immunomodulatory effects in inflammatory and autoimmune diseases, clarifying cardioprotective mechanisms in cardiovascular and cerebrovascular disorders, and facilitating safety evaluation of TCM. Additionally, scRNA-seq bridges TCM's holistic syndrome differentiation with molecular medicine by revealing dynamic correlations between TCM syndromes and cellular heterogeneity. By comparing with Western medical research paradigms, scRNA-seq highlights TCM's distinctive focus on network-driven regulation and holistic balance. CONCLUSION: This review summarizes cutting-edge studies and future directions, emphasizing scRNA-seq's role as a critical bridge in integrating TCM's systemic principles with molecular insights, thereby accelerating TCM and its integration into precision medicine.
-
Identification and targeting of treatment resistant progenitor populations in T-cell Acute Lymphoblastic Leukemia.
Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to cure in T-cell Acute Lymphoblastic Leukemia (T-ALL). Biomarker guided risk stratification and targeted therapy have the potential to improve outcomes in high-risk T-ALL; however, cellular and genetic factors contributing to treatment resistance remain unknown. Previous bulk genomic studies in T-ALL have implicated tumor heterogeneity as an unexplored mechanism for treatment failure. To link tumor subpopulations with clinical outcome, we created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic (CITE-seq/snATAC-seq) analysis to a cohort of 40 cases of T-ALL treated on the Children's Oncology Group AALL0434 clinical trial. The cohort was carefully selected to capture the immunophenotypic diversity of T-ALL, with early T-cell precursor (ETP) and Near/Non-ETP subtypes represented, as well as enriched with both relapsed and treatment refractory cases. Integrated analyses of T-ALL blasts and normal T-cell precursors identified a bone-marrow progenitor-like (BMP-like) leukemia sub-population associated with treatment failure and poor overall survival. The single-cell-derived molecular signature of BMP-like blasts predicted poor outcome across multiple subtypes of T-ALL within two independent patient cohorts using bulk RNA-sequencing data from over 1300 patients. We defined the mutational landscape of BMP-like T-ALL, finding that NOTCH1 mutations additively drive T-ALL blasts away from the BMP-like state. We transcriptionally matched BMP-like blasts to early thymic seeding progenitors that have low NR3C1 expression and high stem cell gene expression, corresponding to a corticosteroid and conventional cytotoxic resistant phenotype we observed in ex vivo drug screening. To identify novel targets for BMP-like blasts, we performed in silico and in vitro drug screening against the BMP-like signature and prioritized BMP-like overexpressed cell-surface (CD44, ITGA4, LGALS1) and intracellular proteins (BCL-2, MCL-1, BTK, NF-κB) as candidates for precision targeted therapy. We established patient derived xenograft models of BMP-high and BMP-low leukemias, which revealed vulnerability of BMP-like blasts to apoptosis-inducing agents, TEC-kinase inhibitors, and proteasome inhibitors. Our study establishes the first multi-omic signatures for rapid risk-stratification and targeted treatment of high-risk T-ALL.
-
CD44 upregulation in chronic liver disease marks the transition to hepatocellular carcinoma and portends poor prognosis.
BACKGROUND: Hepatocellular carcinoma (HCC) often arises from chronic liver disease, but early biomarkers of malignant transformation are lacking. CD44, a transmembrane glycoprotein with multiple isoforms, has been implicated in cancer progression and immune modulation. METHODS: We analysed CD44 expression in mouse models of chronic and acute liver injury and assessed its clinical relevance in human HCC using bulk and single-cell transcriptomic datasets. RESULTS: CD44 and its isoforms v6 and v10 were progressively upregulated in chronic liver injury, peaking in HCC. CD44-positive hepatocytes increased with fibrosis severity and were abundant in murine liver tumours. In human HCC, CD44 expression was significantly elevated compared to non-tumorous liver and was associated with reduced overall survival. CD44high tumours showed enrichment in oncogenic signalling pathways and greater infiltration of immunosuppressive cells, including M2 macrophages and Th2 cells. Single-cell RNA-seq confirmed CD44 expression in both tumour and immune cells, linking it to a protumor immune microenvironment. CONCLUSIONS: CD44 is a promising early biomarker of hepatocarcinogenesis and a potential therapeutic target. Its expression reflects disease progression from fibrosis to cancer and is associated with poor prognosis and immune evasion in HCC.
-
Spatial EGFR Dynamics and Metastatic Phenotypes Modulated by Upregulated EphB2 and Src Pathways in Advanced Prostate Cancer.
Advanced prostate cancer is a very heterogeneous disease reflecting in diverse regulations of oncogenic signaling pathways. Aberrant spatial dynamics of epidermal growth factor receptor (EGFR) promote their dimerization and clustering, leading to constitutive activation in oncogenesis. The EphB2 and Src signaling pathways are associated with the reorganization of the cytoskeleton leading to malignancy, but their roles in regulating EGFR dynamics and activation are scarcely reported. Using single-particle tracking techniques, we found that highly phosphorylated EGFR in the advanced prostate cancer cell line, PC3, was associated with higher EGFR diffusivity, as compared with LNCaP and less aggressive DU145. The increased EGFR activation and biophysical dynamics were consistent with high proliferation, migration, and invasion. After performing single-cell RNA-seq on prostate cancer cell lines and circulating tumor cells from patients, we identified that upregulated gene expression in the EphB2 and Src pathways are associated with advanced malignancy. After dasatinib treatment or siRNA knockdowns of EphB2 or Src, the PC3 cells exhibited significantly lower EGFR dynamics, cell motility, and invasion. Partial inhibitory effects were also found in DU145 cells. The upregulation of parts of the EphB2 and Src pathways also predicts poor prognosis in the prostate cancer patient cohort of The Cancer Genome Atlas. Our results provide evidence that overexpression of the EphB2 and Src signaling pathways regulate EGFR dynamics and cellular aggressiveness in some advanced prostate cancer cells.
-
Multimodal hierarchical classification of CITE-seq data delineates immune cell states across lineages and tissues.
Single-cell RNA sequencing (scRNA-seq) is invaluable for profiling cellular heterogeneity and dissecting transcriptional states, but transcriptomic profiles do not always delineate subsets defined by surface proteins, as in cells of the immune system. Cellular Indexing of Transcriptomes and Epitopes (CITE-seq) enables simultaneous profiling of single-cell transcriptomes and surface proteomes; however, accurate cell type annotation requires a classifier that integrates multimodal data. Here, we describe MultiModal Classifier Hierarchy (MMoCHi), a marker-based approach for classification, reconciling gene and protein expression without reliance on reference atlases. We benchmark MMoCHi using sorted T lymphocyte subsets and annotate a cross-tissue human immune cell dataset. MMoCHi outperforms leading transcriptome-based classifiers and multimodal unsupervised clustering in its ability to identify immune cell subsets that are not readily resolved and to reveal novel subset markers. MMoCHi is designed for adaptability and can integrate annotation of cell types and developmental states across diverse lineages, samples, or modalities.
-
Intranasal booster drives class switching and homing of memory B cells for mucosal IgA response.
Mucosal secretory IgA (sIgA) plays a central role in protecting against the invasion of respiratory pathogen via the upper respiratory tract. To understand how intranasal booster induces mucosal sIgA response in humans, we first used liquid chromatography-tandem mass spectrometry for peptide identification of immunoglobulin (MS Ig-seq) and single-cell B cell receptor sequencing (scBCR-seq) to identify 42 mucosal spike-specific sIgA monoclonal antibodies (mAbs) after intranasal booster. These mucosal sIgA mAbs exhibited enhanced neutralization up to 100-fold against SARS-CoV-2 variants compared with their monomeric IgG and IgA isotypes. Deep sequencing and longitudinal analysis of B cell receptor repertoires revealed that intranasal booster restimulates memory B cells primed by intramuscular vaccination to undergo IgA class switching, somatic hypermutation, and clonal expansion. Single-cell RNA-seq (scRNA-seq) revealed that intranasal booster upregulated the expression of mucosal homing receptors in spike-specific IgA-expressing B cells. This increase coincided with a transient increase of cytokines and chemokines that facilitate B cell recruitment in the nasal mucosa. Our findings demonstrate that intranasal booster can be an effective strategy for inducing upper respiratory mucosal sIgA and establishing mucosal immune protection.
-
Single-cell and spatial transcriptomes reveal the impact of maternal low protein diet on follicular cell composition and ovarian micro-environment in the offspring.
Maternal low protein diet around pregnancy reduces the primordial follicles in offspring ovary. Resolving cellular and molecular mechanisms associated with low protein diet is therefore urgently needed for the guidance of dietary interventions. Here, we utilized single-cell and spatial RNA-seq to create transcriptomic atlases of offspring ovaries from maternal low protein diet mice. Analysis of cell type specific low protein diet associated transcriptional changes revealed increased unfolded protein and decreased oxidative phosphorylation defense as a hallmark of low protein diet effects. Altered pathways included hedgehog signaling in granulosa cells, BMP signaling in theca cells and PTN signaling in early theca cells. Notably, the disordered follicular cell function and ovarian microenvironment may closely corelated with decreased follicular number and quality. Collectively, our findings depict the transcriptomic atlases of the offspring ovary derived from maternal low protein diet group and provide candidate molecular mechanisms underlying the complex ovarian cell changes conferred by low protein diet.