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: 4 877
Page 17 of 488-
Tracing the stemness and malignant transition in a heritable colorectal cancer Lynch Syndrome by single-cell RNA-seq analysis.
BACKGROUND: Lynch Syndrome (LS) is an autosomal dominant disease characterized by germline heterozygous mutations in DNA mismatch repair (MMR) genes. High-risk LS patients may proceed to colorectal cancer (CRC). However, the drivers or biomarkers of LS benign colon tissue approaching malignant CRC are not completely understood. This study aimed to understand the molecular and cellular changes during malignant transition in LS. METHODS: Single-cell RNA sequencing (scRNA-seq) was used to analyze paired fresh biopsy samples from 3 LS patients (carcinoma vs. para-carcinoma, labeled as LS-CA vs. LS-paraCA). Single-nuclear RNA sequencing (snRNA-seq) was used to analyze a frozen biopsy sample of a LS patient. Datasets of Healthy controls and patients diagnosed with sporadic CRC (without LS-related germline or somatic mutations; labeled as nonLS-CRC) were downloaded from the open source. Integrative computational analysis was performed to conclude potential drivers of the malignant transition. Immuno-histo-fluorescence staining (IHF) were also performed for validating the proposed three key markers. RESULTS: In the single-cell atlas, we observed an increase of primitive cancer stem-cells with high expression of biomarkers CEACAM5, BACE2, GPRC5A and OLFM4 in the epithelium of the LS. Both infiltration of immune cells and pathways related to DNA repair biological activity in LS are dramatically increased in carcinoma compared to para-carcinoma. The mutation burden in LS is fundamentally elevated compared to that in healthy controls. Furthermore, T cell and macrophage-related tumor immunity in LS is readily mobilized in carcinomas compared to para-carcinoma. CONCLUSIONS: This study provides single-cell transcriptomic resource using affected tissues from patients with Lynch Syndrome and describes an integrative profile covering the alterations of cancer stem cell markers, mutation burden, and tumor immunity during the malignant transition from latency state to Lynch Syndrome and to colorectal cancer at the single-cell level.
-
Cluster replicability in single-cell and single-nucleus atlases of the mouse brain.
Single-cell RNA sequencing has advanced our understanding of cellular heterogeneity. Ensuring the replicability of identified cell clusters across studies is essential for determining their biological robustness. We assess the replicability of cell clusters identified in two large mouse brain atlases, one generated using single-cell RNA sequencing and the other with single nuclei. Both profile over 4 million cells and group them into over 5,000 clusters. Using transcriptome-wide neighbor voting, we identify 2,009 reciprocally matched cluster pairs with consistent spatial localization and coordinated gene expression, which were also observed in datasets from multiple species. Reciprocal clusters are enriched in the cerebellum, where lower diversity aids replicability, while the hypothalamus's heterogeneity limits agreement. Distinguishing close clusters is much more challenging than differentiating a cluster from most others, especially when using marker genes. By incorporating replicability data, we provide a stronger foundation for investigating the atlas-defined clusters and their biological meaning.
-
Single-cell transcriptome analysis dissects lncRNA-associated gene networks in Arabidopsis.
The plant genome produces an extremely large collection of long noncoding RNAs (lncRNAs) that are generally expressed in a context-specific manner and have pivotal roles in regulation of diverse biological processes. Here, we mapped the transcriptional heterogeneity of lncRNAs and their associated gene regulatory networks at single-cell resolution. We generated a comprehensive cell atlas at the whole-organism level by integrative analysis of 28 published single-cell RNA sequencing (scRNA-seq) datasets from juvenile Arabidopsis seedlings. We then provided an in-depth analysis of cell-type-related lncRNA signatures that show expression patterns consistent with canonical protein-coding gene markers. We further demonstrated that the cell-type-specific expression of lncRNAs largely explains their tissue specificity. In addition, we predicted gene regulatory networks on the basis of motif enrichment and co-expression analysis of lncRNAs and mRNAs, and we identified putative transcription factors orchestrating cell-type-specific expression of lncRNAs. The analysis results are available at the single-cell-based plant lncRNA atlas database (scPLAD; https://biobigdata.nju.edu.cn/scPLAD/). Overall, this work demonstrates the power of integrative single-cell data analysis applied to plant lncRNA biology and provides fundamental insights into lncRNA expression specificity and associated gene regulation.
-
Single-Cell RNA Sequencing Shows Markedly Elevated Immune Cell Proportions in the Endometrium of Women with Endometriosis-A Narrative Review.
Single-cell RNA sequencing is a state-of-the-art approach to decipher the heterogeneity of RNA transcripts in individual cells and identify different cell types in tissues and organs. Its aim is to create a high-resolution cell atlas to better understand organs and diseases. In this narrative review, we focus on the main endometrial cell types and their possible significance in endometriosis. Examination of the normal endometrium (NEM), eutopic endometrium of patients (EUE) and ectopic endometrium (EMS) revealed a predominance of endometrial stromal cells (ESCs), followed by epithelial cells (EECs), immune cells (ICs), endothelial cells (ECs) and pericytes (PVs). Comparison of the NEM with the EUE showed only minor changes in ESC and EEC proportions, but a dramatic increase in ICs in EUE, especially uterine macrophages (uM1). The ESC-IC homeostasis was especially disturbed. In EMS a marked reduction in EEC and NK cell proportions was found, accompanied by a significant increase in ECs and M2 macrophages. Furthermore, in EMS a significant shift from fibroblasts (Fibs) to myofibroblasts (MyoFibs), indicating fibrosis, was reported. Of note, ESC/EEC stem cells were described only very rarely, while nerve cells were not detected. In summary, scRNA-seq provided a good description of the cell proportions in NEM and EUE, but further studies are needed to analyze EMS. In conclusion, strong evidence supports the critical importance of ICs and immune system dysregulation in initiation and of ECs and MyoFibs in angiogenesis and fibrosis, respectively, in the pathogenesis of endometriosis.
-
The Single-Cell Pediatric Cancer Atlas: Data portal and open-source tools for single-cell transcriptomics of pediatric tumors.
The Single-Cell Pediatric Cancer Atlas (ScPCA) Portal is a resource for uniformly processed single-cell and single-nucleus RNA sequencing (RNA-seq) data and de-identified metadata from pediatric tumor samples. Originally comprising data from 10 projects funded by Alex's Lemonade Stand Foundation (ALSF), the Portal currently contains summarized gene expression data for over 700 samples across 55 cancer types from ALSF-funded and community-contributed datasets. Downloads include expression data as SingleCellExperiment or AnnData objects containing raw and normalized counts, principal-component analysis (PCA) and uniform manifold approximation and projection (UMAP) coordinates, automated cell-type annotations, and copy-number variation estimates, along with summary reports. Some samples have additional data from bulk RNA-seq, spatial transcriptomics, and/or feature barcoding (e.g., CITE-seq) included in the download. All data on the Portal were uniformly processed using scpca-nf, an efficient and open-source Nextflow workflow that uses alevin-fry to quantify gene expression. Comprehensive documentation, including file descriptions and a getting-started guide, are available online.
-
Unraveling spermatogenesis: A single-cell genomics perspective.
Spermatogenesis is a highly coordinated male developmental process essential for passing on genetic information and fertility. The process features a series of complex cellular and genomic transitions. The main objective of this review is to provide a synthesis of changes single-cell genomics have brought to the male germline. This review begins with an account of the journey from rudimentary, low resolution, and throughput microarray technologies to the advanced and sophisticated, high throughput single-cell RNA sequencing (scRNA-seq) technologies that have provided the means for the generation of extensive and comprehensive "cell atlases" of the testis. The review focuses on the resolution of long-standing controversies associated with the spermatogonial stem cells (SSCs) niche regarding continuum of germ cell differentiation, and germ cell differentiation and stem cell specification. The frontiers of single-cell based DNA techniques such as Single-Cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) and single-cell DNA methylation will then be discussed. We focus on the perinatal period crucial for the epigenetic priming of the foundational stem cell pool and chromatin remodeling that facilitates the histone-to-protamine transition. The regenerative capacity of the germline and the single-cell identified subsets and metabolic gates that are capable of restoring the ability to conceive post-injury tissues are also explored. Finally, we will go over the prospective views on the use of multi-omics and new spatial transcriptomics. These tools not only provide molecular components of interest within the cells, but also the cellular constituents of the seminiferous tubule and their spatial location within the tubule. This novel information will help translate the molecular discovery into potential clinical applications for male infertility treatment.
-
Unravelling cell heterogeneity and gene regulation mechanisms in multiple myeloma through single-cell RNA-seq.
Multiple myeloma (MM) is the second most common blood cancer in the world, yet its genetic pathology is not fully understood and MM cells have highly heterogeneous regulatory mechanisms. Single-cell RNA-Sequencing (scRNA-Seq) technologies provide an unprecedented opportunity to investigate cell heterogeneity and understand regulatory mechanisms at the single-cell level. Four MM scRNA-Seq datasets were retrieved from the public domain containing 597, 172, 477, and 51,840 cells, respectively. First, they were integrated and jointly analyzed to accurately identify 24 MM cell clusters, using a normal hematopoiesis cells atlas as a control. Then we predicted 651 regulons within the 24 MM cell clusters. The identified regulons can substantially improve the elucidation of heterogeneous gene regulation mechanisms across various cell clusters, and hence can serve as a reference for diagnosis in MM.
-
Single-cell transcriptional and epigenomic landscape of human blood immune cells across the lifespan.
The dynamic changes in immune cell composition throughout the human lifespan remain poorly understood. Here, we performed single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing on peripheral blood mononuclear cells from healthy donors, spanning mid-fetal to late adulthood. Our findings revealed age-associated reprogramming across lymphoid and myeloid lineages, with T cells undergoing the most significant transcriptional remodeling. Notably, ITGB1+CD8+ effector memory T cells played a protective role in young adulthood. Furthermore, an immunosuppressive AREG+ natural killer (NK) cell subset was enriched in early childhood, exhibiting low expression of cytotoxic and activating markers and high expression of inhibitory molecules. Additionally, fetal-derived XCL2+CD56bright NK cells show an upregulation of inhibitory receptor KLRC1, while IL1Bhi monocytes increased in aging, contributing to inflammaging. Overall, our study provides a comprehensive single-cell atlas of peripheral immune cell dynamics across the human lifespan and reveals various age-related signatures, offering insights into immune aging and its role in age-related diseases.
-
Pan-cancer single-cell atlases of mouse and human tumor-associated dendritic cells.
Dendritic cells (DCs) are critical inducers of anti-tumor immunity. To achieve a comprehensive mapping of mouse and human DC subsets and states in a cancer context, here we generate pan-cancer mouse and human tumor-associated DC (TADC) scRNA-seq atlases, encompassing 14 mouse tumor models and 10 human cancer types, within which we identify several lineage-defined DC subsets along with maturation/functional states. We show that TADCs acquire an inflammatory profile with tumor progression and that tumor-mediated reprogramming occurs within the DCs from lymph nodes of tumor-bearing mice. Importantly, we demonstrate that TADCs are broadly conserved between mice and humans, although species-specific differences may exist in some subsets and states. Moreover, we present a comprehensive assessment of how different human TADC clusters associate with patient survival outcomes. Overall, we provide an in-depth characterization of the TADC compartment in mouse and human cancers, which can improve our understanding of the tumor microenvironment and contribute to the development of new anti-cancer therapies.
-
Identification of a Cancer Stem Cell-Related Gene Signature in Hepatocellular Carcinoma Based on Single-Cell RNA-Seq and Bulk RNA-Seq Analysis.
Cancer stem cells (CSCs) are a heterogeneous group of tumor cells that play a significant role in tumorigenesis, therapeutic resistance, and recurrence in liver hepatocellular carcinoma (LIHC). This study combines clinical data sets from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) with bulk RNA sequencing data. This study also features the GSE156625 single-cell RNA sequencing (scRNA) data set from the GEO to explore the prognostic significance of CSC biomarkers (BCSCs) in LIHC. In this research, we introduce a developed prognostic risk model that relies on nine specific BCSCs, including ADM, CCL5, CD274, DLGAP5, HOXD9, IGF1, S100A9, SOCS2, and TNFRSF11B. It was found that high-risk patients experience shorter overall survival rates when compared to low-risk patients. Additionally, the study characterized the composition of immune cells within the tumor microenvironment (TME) and revealed significant variations in gene-expression levels and mutation rates between different risk groups. The model suggests that liver cancer progression might be driven by immune evasion independent of PD-L1 and highlights the potential of the low-risk BCSC group being sensitive to various treatments. Our findings offer a promising foundation for personalized LIHC therapy and highlight the need for further experimental validation of the roles of these CSCs in disease progression.