1,721,017 research outputs found
Single-cell rna sequencing in parkinson’s disease
Full text linkSingle-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have enhanced the understanding of the molecular pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). Nonetheless, their application in PD has been limited due mainly to the technical challenges resulting from the scarcity of postmortem brain tissue and low quality associated with RNA degradation. Despite such challenges, recent advances in animals and human in vitro models that recapitulate features of PD along with sequencing assays have fueled studies aiming to obtain an unbiased and global view of cellular composition and phenotype of PD at the single-cell resolution. Here, we reviewed recent sc/snRNA-seq efforts that have successfully characterized diverse cell-type populations and identified cell type-specific disease associations in PD. We also examined how these studies have employed computational and analytical tools to analyze and inter-pret the rich information derived from sc/snRNA-seq. Finally, we highlighted important limitations and emerging technologies for addressing key technical challenges currently limiting the integration of new findings into clinical practice
An integrated single-cell transcriptomic dataset for non-small cell lung cancer
No full textAs single-cell RNA sequencing (scRNA-seq) has emerged as a great tool for studying cellular heterogeneity within the past decade, the number of available scRNA-seq datasets also rapidly increased. However, reuse of such data is often problematic due to a small cohort size, limited cell types, and insufficient information on cell type classification. Here, we present a large integrated scRNA-seq dataset containing 224,611 cells from human primary non-small cell lung cancer (NSCLC) tumors. Using publicly available resources, we pre-processed and integrated seven independent scRNA-seq datasets using an anchor-based approach, with five datasets utilized as reference and the remaining two, as validation. We created two levels of annotation based on cell type-specific markers conserved across the datasets. To demonstrate usability of the integrated dataset, we created annotation predictions for the two validation datasets using our integrated reference. Additionally, we conducted a trajectory analysis on subsets of T cells and lung cancer cells. This integrated data may serve as a resource for studying NSCLC transcriptome at the single cell level
Comprehensive Single-Cell Transcriptomic Atlas of the Mouse Pons and Medulla
No full textThe pons and medulla, key regions of the hindbrain within the brainstem, regulate a wide range of complex behaviors, ranging from motor control to autonomic regulation and reflexes. As the central hub of neural projections and gut-to-brain communication, the cellular diversity that supports these functions remains ambiguous. To address this, we integrated eight single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) datasets from mouse brains. We constructed a large-scale single-cell atlas encompassing 318,522 single cells from different sub-regions of the pons and medulla. Using a rigorous metadata standardization and annotation approach, we identified 45 cell types that span major populations and exhibit subtype-specific variability. We observed high diversity among neuronal populations, while non-neuronal cells were dominated by glial and vascular cells, each with unique transcriptional profiles. This atlas serves as the foundational resource for exploring region-specific cellular diversity in the pons and medulla, enabling comparative analyses for future studies
SRSF7 downregulation induces cellular senescence through generation of MDM2 variants
Full text linkAlternative splicing (AS) enables a pre-mRNA to generate different functional protein variants. The change in AS has been reported as an emerging contributor to cellular senescence and aging. However, it remains to be elucidated which senescent AS variants are generated in and regulate senescence. Here, we observed commonly down-regulated SRSF7 in senescent cells, using publicly available RNA-seq datasets of several in vitro senescence models. We further confirmed SRSF7 deregulation from our previous microarray datasets of time-series replicative senescence (RS) and oxidative stress-induced senescence (OSIS) of human diploid fibroblast (HDF). We validated the time-course changes of SRSF mRNA and protein levels, developing both RS and OSIS. SRSF knockdown in HDF was enough to induce senescence, accompanied by p53 protein stabilization and MDM2 variants formation. Interestingly, expression of MDM2 variants showed similar patterns of p53 expression in both RS and OSIS. Next, we identified MDM2-C as a key functional AS variant generated specifically by SRSF7 depletion. Finally, we validated that MDM2-C overexpression induced senescence of HDF. These results indicate that SRSF7 down-regulation plays a key role in p53-mediated senescence by regulating AS of MDM2, a key negative regulator of p53, implying its critical involvement in the entry into cell senescence
Correspondence to editorial on “Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma”
Full text linkPhosphorylation analysis of the Hippo-YAP pathway using Phos-tag
No full textPhosphorylation is an essential regulatory mechanism in cells that modifies diverse substrates, such as proteins, carbohydrates, lipids, and nucleotides. Protein phosphorylation regulates function, subcellular localization, and protein-protein interactions. Protein kinases and phosphatases catalyze this reversible mechanism, subsequently influencing signal transduction. The dysregulation of protein phosphorylation leads to many diseases, such as cancer, neurodegenerative diseases, and metabolic diseases. Therefore, analyzing the phosphorylation status and identifying protein phosphorylation sites are critical for elucidating the biological functions of specific phosphorylation events. Unraveling the critical phosphorylation events associated with diseases and specific signaling pathways is promising for drug discovery. To date, highly accurate and sensitive approaches have been developed to detect the phosphorylation status of proteins. In this review, we discuss the application of Phos-tag to elucidate the biological functions of Hippo pathway components, with emphasis on the identification and quantitation of protein phosphorylation under physiological and pathological conditions. SIGNIFICANCE: We here provide a comprehensive overview of Phos-tag technique-based strategies to identify phosphorylated proteins at the cellular level in the Hippo-YAP pathway that comprises a major driving force for cellular homeostasis. We clarify the links of applying Phos-tag in elucidating the biological functions of the Hippo pathway components with particular attention to the identification and quantitation of protein phosphorylation under physiological and pathological conditions. We believe that our paper will make a significant contribution to the literature because these detailed phosphorylation modifications and functional diversity of the Hippo pathway components in physiological and pathological processes are only beginning to come to the fore, highlighting the potential for discovering new therapeutic targets. Moreover, this line of research can provide further insight into the inextricable link between phos-tag applications as a molecular tool and cellular signaling modality, offering new directions for an integrated research program toward understanding cellular regulation at the molecular level. Given the broad research and practical applications, we believe that this paper will be of interest to the readership of your journal
A single-cell RNA sequencing dataset of peripheral blood cells in long COVID patients on herbal therapy
No full textFollowing the coronavirus disease 2019 (COVID-19) pandemic, the rise of long COVID, characterized by persistent respiratory and cognitive dysfunctions, has become a significant health concern. This leads to an increased role of complementary and alternative medicine in addressing this condition. However, our comprehension of the effectiveness and safety of herbal medicines for long COVID remains limited. Here, we present a single-cell RNA sequencing (scRNA-seq) dataset of peripheral whole blood cells derived from participants in a clinical study involving three commercially available herbal medicines, targeting fatigue and brain fog in long COVID. The dataset comprises 181,205 quality control (QC)-passed cells, along with clinical metadata, enabling a comparative analysis of immune cell populations before and after treatment. To ensure the technical validity of our dataset, we implemented rigorous quality checks throughout stages of the study, including sample preparation, sequencing, and bioinformatic data analysis levels. This transcriptomic data may serve as a resource to deepen our insights into the role of herbal medicines in management of long COVID
Single-cell insights into the dynamic tumor microenvironment changes during immunotherapy of non-small cell lung cancer
Full text linkPublisher Correction: Multi-omic analysis of selectively vulnerable motor neuron subtypes implicates altered lipid metabolism in ALS
No full textIn the version of this article originally published, there were errors in Fig. 1i–k. The x-axis labels now reading “FL1 (HB9::GFP) →” initially appeared as “FL1 (PHOX2B::GFP) →.” The changes have been made to the online version of the article. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2021
Matrisomics: Beyond the extracellular matrix for unveiling tumor microenvironment
Full text linkThe matrisome, a group of proteins constituting or interacting with the extracellular matrix (ECM), has garnered attention as a potent regulator of cancer progression. An increasing number of studies have focused on cancer matrisome utilizing diverse -omics approaches. Here, we present diverse patterns of matrisomal populations within cancer tissues, exploring recent -omics studies spanning different ‘-omics’ levels (epigenomics, genomics, transcriptomics, and proteomics), as well as newly developed sequencing techniques such as single-cell RNA sequencing and spatial transcriptomics. Some matrisome genes showed uniform patterns of upregulated or downregulated expression across various cancers, while others displayed different expression patterns according to the cancer types. This matrisomal dysregulation in cancer was further examined according to their originating cell type and spatial location in the tumor tissue. Experimental studies were also collected to demonstrate the identified roles of matrisome genes during cancer progression. Interestingly, many studies on cancer matrisome have suggested matrisome genes as effective biomarkers in cancer research. Although the specific mechanisms and clinical applications of cancer matrisome have not yet been fully elucidated, recent techniques and analyses on cancer matrisomics have emphasized their biological importance in cancer progression and their clinical implications in deciding the efficacy of cancer treatment
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