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: 4 928
Page 242 of 493-
A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex.
The molecular organization of the human neocortex historically has been studied in the context of its histological layers. However, emerging spatial transcriptomic technologies have enabled unbiased identification of transcriptionally defined spatial domains that move beyond classic cytoarchitecture. We used the Visium spatial gene expression platform to generate a data-driven molecular neuroanatomical atlas across the anterior-posterior axis of the human dorsolateral prefrontal cortex. Integration with paired single-nucleus RNA-sequencing data revealed distinct cell type compositions and cell-cell interactions across spatial domains. Using PsychENCODE and publicly available data, we mapped the enrichment of cell types and genes associated with neuropsychiatric disorders to discrete spatial domains.
-
Identification of ZEB2 as an Immune-Associated Gene in Endometrial Carcinoma and Associated with Macrophage Infiltration by Bioinformatic Analysis.
Endometrial cancer (EC) is the most common gynecological tumor arising from the endometrium. In this study, we use a published single-cell transcriptome profile of endometrial carcinoma (EC) to reveal the composition of immune cells and found an immunosuppressive environment since the presence of macrophage subtype M2 and exhausted CD8+ T cell markers. We focused on ZEB2 (Zinc finger E-box binding homeobox 2), a well-known player in epithelial to mesenchymal transition process, and we showed that ZEB2 is exclusively expressed in immune cells in single-cell transcriptome and, at the same time, downregulated in TCGA-UCEC (The Cancer Genome Atlas-Uterine Corpus Endometrial Carcinoma) bulk RNA-seq data and negatively associated with tumor purity. Loss of ZEB2 protein in EC in normal endometrium and EC samples was validated in samples using immunohistochemistry (IHC) from HPA (Human Protein Atlas) database. Furthermore, we found ZEB2 was associated with immune infiltrations especially for macrophage using TIMER 2.0. Interestingly, ZEB2 prognostic significance differed under various macrophage and Th2 helper cell content using Kaplan-Meier Plotter analysis. More importantly, we showed that over 11% EC patients have somatic mutations of ZEB2 in EC samples collected from cBioportal and they have a lower body weight, earlier diagnosis age, and better overall survival and disease-free survival status compared with the unaltered group. Analysis in TIMER2.0 suggested that ZEB2 mutation would possibly change the composition of tumor-infiltrating lymphocytes. Taken together, by combining the results from single-cell data, bulk TCGA RNA-seq, and other online bioinformatic tools, we provided evidence that ZEB2 might have a unique role in the immune environment of EC. These results would provide a better insight into the pathogenetic process and ZEB2 might further be used an immunotherapeutic target of EC.
-
Transcriptomic atlas of midbrain dopamine neurons uncovers differential vulnerability in a Parkinsonism lesion model.
Midbrain dopamine (mDA) neurons comprise diverse cells with unique innervation targets and functions. This is illustrated by the selective sensitivity of mDA neurons of the substantia nigra compacta (SNc) in patients with Parkinson's disease, while those in the ventral tegmental area (VTA) are relatively spared. Here, we used single nuclei RNA sequencing (snRNA-seq) of approximately 70,000 mouse midbrain cells to build a high-resolution atlas of mouse mDA neuron diversity at the molecular level. The results showed that differences between mDA neuron groups could best be understood as a continuum without sharp differences between subtypes. Thus, we assigned mDA neurons to several 'territories' and 'neighborhoods' within a shifting gene expression landscape where boundaries are gradual rather than discrete. Based on the enriched gene expression patterns of these territories and neighborhoods, we were able to localize them in the adult mouse midbrain. Moreover, because the underlying mechanisms for the variable sensitivities of diverse mDA neurons to pathological insults are not well understood, we analyzed surviving neurons after partial 6-hydroxydopamine (6-OHDA) lesions to unravel gene expression patterns that correlate with mDA neuron vulnerability and resilience. Together, this atlas provides a basis for further studies on the neurophysiological role of mDA neurons in health and disease.
-
Understanding the development of oral epithelial organs through single cell transcriptomic analysis.
During craniofacial development, the oral epithelium begins as a morphologically homogeneous tissue that gives rise to locally complex structures, including the teeth, salivary glands and taste buds. How the epithelium is initially patterned and specified to generate diverse cell types remains largely unknown. To elucidate the genetic programs that direct the formation of distinct oral epithelial populations, we mapped the transcriptional landscape of embryonic day 12 mouse mandibular epithelia at single cell resolution. Our analysis identified key transcription factors and gene regulatory networks that define different epithelial cell types. By examining the spatiotemporal patterning process along the oral-aboral axis, our results propose a model in which the dental field is progressively confined to its position by the formation of the aboral epithelium anteriorly and the non-dental oral epithelium posteriorly. Using our data, we also identified Ntrk2 as a proliferation driver in the forming incisor, contributing to its invagination. Together, our results provide a detailed transcriptional atlas of the embryonic mandibular epithelium, and unveil new genetic markers and regulators that are present during the specification of various oral epithelial structures.
-
Single-cell RNA sequencing in vision research: Insights into human retinal health and disease.
Gene expression provides valuable insight into cell function. As such, vision researchers have frequently employed gene expression studies to better understand retinal physiology and disease. With the advent of single-cell RNA sequencing, expression experiments provide an unparalleled resolution of information. Instead of studying aggregated gene expression across all cells in a heterogenous tissue, single-cell technology maps RNA to an individual cell, which facilitates grouping of retinal and choroidal cell types for further study. Single-cell RNA sequencing has been quickly adopted by both basic and translational vision researchers, and single-cell level gene expression has been studied in the visual systems of animal models, retinal organoids, and primary human retina, RPE, and choroid. These experiments have generated detailed atlases of gene expression and identified new retinal cell types. Likewise, single-cell RNA sequencing investigations have characterized how gene expression changes in the setting of many retinal diseases, including how choroidal endothelial cells are altered in age-related macular degeneration. In addition, this technology has allowed vision researchers to discover drivers of retinal development and model rare retinal diseases with induced pluripotent stem cells. In this review, we will overview the growing number of single-cell RNA sequencing studies in the field of vision research. We will summarize experimental considerations for designing single-cell RNA sequencing experiments and highlight important advancements in retinal, RPE, choroidal, and retinal organoid biology driven by this technology. Finally, we generalize these findings to genes involved in retinal degeneration and outline the future of single-cell expression experiments in studying retinal disease.
-
Comparative transcriptomics identifies conserved gene signatures defining megakaryocyte development states across species.
Megakaryocytes and platelets are essential for hemostasis, immune regulation and hematopoietic niche maintenance, while also promoting thrombosis. Comprehensive characterization of late-stage megakaryocyte maturation in mammals using single-cell RNA-sequencing (scRNA-Seq) remains challenging due to the large size of megakaryocytes and the low RNA content of platelets. Although zebrafish thrombocytes are functionally analogous and retain high transcriptional activity at maturity, their transcriptional similarities to mammals have not been systematically defined. To address this, we generated a single-cell transcriptomic atlas spanning the full developmental trajectory of zebrafish thrombocytes, demonstrating that lineage progression is continuous and functionally coordinated. Cross-species comparison with human and mouse datasets defined conserved differentiation stages and gene modules of the megakaryocyte-platelet lineage, indicating evolutionary conservation of lineage development at single-cell resolution. Moreover, we identified a gene set (M3pan-PLT) that marks a platelet-like transcriptional state in zebrafish thrombocytes, supporting their transcriptomic analogy to mammalian platelets. Finally, bulk transcriptomic analyses using these conserved gene signatures demonstrated their ability to capture physiological megakaryocyte states, as well as disease-associated transcriptional alterations in acute megakaryoblastic leukemia. Together, our study defines a conserved and continuous developmental framework of megakaryocytes at single-cell resolution and establishes zebrafish thrombocytes as a transcriptionally conserved model for dissecting late-stage megakaryocyte-platelet biology.
-
Single‑cell RNA sequencing reveals fibroblast heterogeneity and identifies CLOCK as a key regulator in fibrotic skin diseases.
Fibrosis, characterized by excessive extracellular matrix (ECM) accumulation and fibroblast proliferation, significantly contributes to global morbidity and mortality, affecting millions worldwide. Despite its prevalence, the mechanisms underlying fibrotic skin diseases remain poorly understood, and effective treatments are scarce. This study leverages single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of fibroblasts in fibrotic skin diseases, including normal skin, scar, keloid, and scleroderma. Through comprehensive analysis of scRNA-seq data from public repositories, we identified distinct fibroblast subpopulations specific to each fibrotic condition. Notably, pivotal regulators for each sub-fibroblast cluster were discovered: IRF4 for scar, CLOCK for keloid, RUNX3 for scleroderma, and HOXC4 for normal skin. Further, CLOCK was found to be predominantly expressed in keloid tissues, with its upregulation enhancing fibroblast proliferation and migration in vitro. Analysis of The Cancer Genome Atlas (TCGA) data revealed that CLOCK and its regulon genes were upregulated in skin cutaneous melanoma and even more so in metastatic tumors. Our findings underscore the utility of scRNA-seq in dissecting the cellular complexity of fibrotic skin diseases and highlight potential therapeutic targets. This study not only advances our understanding of fibroblast heterogeneity in fibrosis but also opens avenues for targeted therapeutic strategies, moving closer to personalized medicine for fibrotic diseases.
-
Time-resolved single-cell transcriptomics maps zebrafish heart development.
Cardiac development is a process where bilateral precursors come together to form a tube that matures into a complex multi-chambered organ. Despite advances in single-cell RNA sequencing technology, a comprehensive analysis of zebrafish heart development from early to late stages is still lacking. We profiled over 34,000 cells from zebrafish hearts spanning ten developmental stages from 25 h to 60 days post-fertilization. We identified and subclustered all known cardiac cell types, revealing distinct proliferation dynamics and uncovering an additional peak in cardiomyocyte proliferation at 14 days post-fertilization. We analyzed the cardiac interactome, focusing on ligand-receptor interactions between the myocardium and endocardium. By investigating later stages, we discovered several marker genes that are enriched in compact or trabecular layer cardiomyocytes including bcam, kcnj14, and kcnj5. We also identified kcnj3b as a specific pacemaker gene. This zebrafish heart atlas enhances our understanding of vertebrate heart development and represents a valuable resource for future studies.
-
NBAtlas: A harmonized single-cell transcriptomic reference atlas of human neuroblastoma tumors.
Neuroblastoma, a rare embryonic tumor arising from neural crest development, is responsible for 15% of pediatric cancer-related deaths. Recently, several single-cell transcriptome studies were performed on neuroblastoma patient samples to investigate the cell of origin and tumor heterogeneity. However, these individual studies involved a small number of tumors and cells, limiting the conclusions that could be drawn. To overcome this limitation, we integrated seven single-cell or single-nucleus datasets into a harmonized cell atlas covering 362,991 cells across 61 patients. We use this atlas to decipher the transcriptional landscape of neuroblastoma at single-cell resolution, revealing associations between transcriptomic profiles and clinical outcomes within the tumor compartment. In addition, we characterize the complex immune-cell landscape and uncover considerable heterogeneity among tumor-associated macrophages. Finally, we showcase the utility of our atlas as a resource by expanding it with additional data and using it as a reference for data-driven cell-type annotation.
-
Systemic and single cell level responses to 1 nm size biomaterials demonstrate distinct biological effects revealed by multi-omics atlas.
Although ultra-small nanoclusters (USNCs, < 2 nm) have immense application capabilities in biomedicine, the investigation on body-wide organ responses towards USNCs is scant. Here, applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues, we systematically evaluate the interactions between the host and calcium phosphate (CaP) USNCs at the organism level. Combining single-cell mass cytometry, and magnetic luminex assay results, we identify dynamic immune responses to CaP USNCs at the single cell resolution. The innate immune is initially activated and followed by adaptive immune activation, as evidenced by dynamic immune cells proportions. Furthermore, using Nano Genome Atlas of multi-tissues, we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney. Moreover, based on the immunological response profiles, histological evaluation of major organs and local tissue, and a body-wide transcriptomics, we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection. Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.