Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus
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ABSTRACT:
PROVIDER: PRJNA634564 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11833371_1.fastq.gz | Fastqsanger.gz | |||
| SRR11833371_2.fastq.gz | Fastqsanger.gz | |||
| SRR11833372_1.fastq.gz | Fastqsanger.gz | |||
| SRR11833372_2.fastq.gz | Fastqsanger.gz | |||
| SRR11833373_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: It has been observed that the drug verteporfin (VP), a known disruptor of YAP-TEAD signaling, causes cell rounding and changes in phenotype and biosynthesis in human nucleus pulposus cells. In this study the time-dependent effects of VP treatment on the transcriptome of human NP cells was explored. Methods: mRNA profiles of NP cells treated for 24 hours, 48 hours, or 4 days with VP or vehicle (DMSO) control were generated for cells from 3 adult human tissue samples, using Illumina NovaSeq. Unaligned reads were trimmed based on quality score (minimum quality level (Phred) = 20, minimum read length = 25) and aligned to the whole human genome (STAR 2.6.1d; hg19) using Partek Flow software. This software suite was also used to calculate the counts/normalized counts of genes and to perform gene specific analysis (GSA), principle component analysis (PCA), hierarchical clustering, and gene set enrichment. Differentially regulated genes were considered to be those with a fold change value (VP/DMSO) for a given time point that was greater than or equal to 2 or less than or equal to negative 2 and a FDR-adjusted p-value of less than or equal to 0.05. Results: Using a data analysis workflow buit in Partek Flow, we identified 1810 differentially regulated genes at 24 hours, 4287 differentially regulated genes at 48 hours, and 9272 differentially regulated genes at 4 days. Hierarchical clustering and PCA analysis demonstrated clustering of the data by patient and time point, but separation by treatment group. We further observed that while generally the expression of fibroblastic markers decreased with VP treatment, a number of markers of NP phenotype were increased. We also identified enriched gene sets (ex. 2026 at the 4 day time point) which represented a variety of cellular components, processes, and functions potentially implicated by VP treatment. Conclusions: The data from this RNA-sequencing demonstrate that VP treatment which induces cell rounding in NP cells was also accompanied by pronounced and time-dependent changes in the transcriptome of adult NP cells in culture. The enriched gene sets and differentially regulated genes suggest a major role for cell adhesion, cytoskeletal remodeling, vacuolar lumen, and M APK activity in the NP phenotypic and functional response to changes in cell shape.
2020-08-03 | GSE151090 | GEO
Project description:Synovial and bone marrow mesenchymal stem cells after intradiscally injection show regenerative effects of nucleus pulposus. Microarray analyses of rats were performed to investigate the closeness of the gene profiles between the nucleus pulposus cells and the synovial or bone marrow mesenchymal stem cells. To investigate interaction between synovial mesenchymal stem cells and nucleus pulposus cells, human synovial mesenchymal stem cells and rat nucleus pulposus cells were co-cultured, and species specific microarray were performed. Synovium of knee joints, bone marrow and nucleus pulposus were harvested from rat or human, and cells were isolated for RNA extraction and hybridization on Affymetrix microarrays. To compare the gene profiles each other, isolated cells were mono-cultured respectively, and human synovial mesenchymal stem cells and rat nucleus pulposus cells were co-cultured.
2010-10-11 | E-GEOD-24612 | biostudies-arrayexpress
Project description:MicroRNAs expression profiling of human nucleus pulposus cells derived from patients with disc degeneration in comparison with those derived from patients with scoliosis as control. Two-condition experiment: control nucleus pulposus cells vs. degenerative nucleus pulposus cells. Biological replicates: 3 control, 3 degenerated, independently harvested. Four replicates per array. The supplementary file 'GSE19943_fold_pvalue.txt' contains fold-changes and p-values.
2012-01-01 | E-GEOD-19943 | biostudies-arrayexpress
Project description:To identify PPP1CA interactome in human nucleus pulposus cell
2023-10-24 | PXD042397 | Pride
Project description:Failure of intervertebral disc components, e.g. the nucleus pulposus causes intervertebral disc disease and associated low-back pain. Despite the high prevalence of disc disease, the changes in intervertebral disc cells and their regenerative potential with ageing and degeneration are not fully elucidated. Understanding the cell lineage, cell differentiation and maintenance of nucleus pulposus may have therapeutic application for the regeneration of degenerative disc, with significant impact for healthy ageing. Here we found that TAGLN expressing cells are present in human healthy nucleus pulposus, but diminish in degenerative disc. By lineage analyses in mice, we found cells in the nucleus pulposus are derived from a peripherally located population of notochord-derived Tagln expressing cells (PeriNP cells). The PeriNP cells are proliferative and can differentiate into the inner part of the nucleus pulposus. The Tagln+ cells and descendants diminish during aging and puncture induced disc degeneration. The maintenance and differentiation of PeriNP cells is partially regulated by Smad4 dependent signaling. Removal of Smad4 by nucleus pulposus specific Cre (Foxa2mNE-Cre), results in decreased Tagln+ cells and abnormal disc morphology, leading to disc degeneration. Our findings propose that the PeriNP Tagln expressing cells are a pool of notochord-derived progenitors that are important for maintenance of the nucleus pulposus and provide insights for regenerative therapy against intervertebral disc degeneration.
2024-05-14 | GSE186549 | GEO
Project description:To investigate whether SUV39H2 binds to PPP1CA in nucleus pulposus cells
2023-10-24 | PXD042152 | Pride
Project description:Assessment of the putative differential gene expression profiles in high osmolality-treated bovine nucleus pulposus intervertebral disc cells for a short (5 h) and a long (24 h) time period. Identification of novel genes up- or down-regulated as an early or a late response to hyperosmotic stress. A 5 and 24 h-hyperosmotic treatment of nucleus pulposus cells led to transcriptional changes in >100 and 200 genes, respectively. Nucleus pulposus intervertebral disc cells were exposed to hyperosmotic stress for 5 and 24 h before RNA extraction and transcriptomics analysis. Three biological replicates were tested for each condition. Selected genes found to be differentially expressed were validated by RT-qPCR. Functional experiments were performed in order to assess the role of specific proteins encoded by genes found to be up-regulated in the osmo-reguatory response of intervertebral disc cells.
2015-06-19 | E-GEOD-59485 | biostudies-arrayexpress
Project description:Synovial and bone marrow mesenchymal stem cells after intradiscally injection show regenerative effects of nucleus pulposus. Microarray analyses of rats were performed to investigate the closeness of the gene profiles between the nucleus pulposus cells and the synovial or bone marrow mesenchymal stem cells. To investigate interaction between synovial mesenchymal stem cells and nucleus pulposus cells, human synovial mesenchymal stem cells and rat nucleus pulposus cells were co-cultured, and species specific microarray were performed.
2010-10-11 | GSE24612 | GEO
Project description:Cells of the nucleus pulposus (NP) are essential contributors to extracellular matrix synthesis and function of the intervertebral disc. With age and degeneration, the NP becomes stiffer and more dehydrated, which is associated with a loss of phenotype and biosynthetic function for its resident NP cells. Also, with aging, the NP cell undergoes substantial morphological changes from a rounded shape with pronounced vacuoles in the neonate and juvenile, to one that is more flattened and spread with a loss of vacuoles. Here, we make use of the clinically relevant pharmacological treatment verteporfin (VP), previously identified as a disruptor of yes-associated protein-TEA domain family member-binding domain (TEAD) signaling, to promote morphological changes in adult human NP cells in order to study variations in gene expression related to differences in cell shape. Treatment of adult, degenerative human NP cells with VP caused a shift in morphology from a spread, fibroblastic-like shape to a rounded, clustered morphology with decreased transcriptional activity of TEAD and serum-response factor. These changes were accompanied by an increased expression of vacuoles, NP-specific gene markers, and biosynthetic activity. The contemporaneous observation of VP-induced changes in cell shape and prominent, time-dependent changes within the transcriptome of NP cells occurred over all timepoints in culture. Enriched gene sets with the transition to VP-induced cell rounding suggest a major role for cell adhesion, cytoskeletal remodeling, vacuolar lumen, and MAPK activity in the NP phenotypic and functional response to changes in cell shape.
| S-EPMC7770208 | biostudies-literature
Project description:In order to discover the cell type in nucleus pulposus and find the cell type specific genetic change during intervertebral disc degeneration, we applied single cell RNA sequencing of nucleus pulposus tissue from degenerated and non-degenerated disc.
2023-12-31 | GSE153066 | GEO