The single-cellsequencing of purified wild type rat intervertebral disc (IVD) cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE154884 | GEO | 2020/07/23
REPOSITORIES: GEO
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Project description:We report the single-cell RNA-seq (scRNA-seq) data for human neonatal and adult human intervertebral disc (IVD) scRNA-seq. We sequenced cells harvested from three IVDs of a neonatal baby and one IVD from an adult cadaver.
2021-12-07 | GSE189916 | GEO
Project description:Purpose: We used single-cell RNA-sequencing analysis of degenerating tissues of the rat IVD following lumbar disc puncture Methods: Two control, uninjured IVDs (L2-3, L3-4) and two degenerated, injured IVDs (L4-5, L5-6) from each animal were examined either at the two- or eight-week post-operative time points. The cells from these IVDs were extracted and transcriptionally profiled at the single-cell resolution Results: Unsupervised cluster analysis revealed the presence of four known cell types in both non-degenerative and degenerated IVDs based on previously established gene markers: IVD cells, endothelial cells, myeloid cells, and lymphoid cells. As a majority of cells were associated with the IVD cell cluster, sub-clustering was used to further identify the cell populations of the nucleus pulposus, inner and outer annulus fibrosus Conclusions: . Differential gene expression analysis revealed multiple distinct cell types from the myeloid and lymphoid lineages, most notably macrophages and B lymphocytes, and demonstrated a high degree of immune specificity during degeneration. In addition to the heterogenous infiltrating immune cell populations in the degenerating IVD, the increased number of cells in the AF sub-cluster expressing Ngf and Ngfr, encoding for p75NTR, suggest that NGF signaling may be one of the key mediators of the IVD crosstalk between immune and neuronal cell populations
2022-08-19 | GSE211407 | GEO
Project description:Intervertebral disc (IVD) is often the cause of low back pain. Degeneration occurs with age and is accompanied by extracellular matrix (ECM) depletion, culminating in nucleus pulpous (NP) extrusion and IVD destruction. Although the changes that occur with ageing in the IVD have been under study, not much attention has been given to ECM remodelling during normal development. Therefore, a thorough study of ECM composition and a comprehensive view on how this microenvironment is affected in normal ageing conditions is needed, to better understand the processes involved in IVD development and in age-associated degeneration. We have compared the NP matrisome of bovine IVDs from foetus, young and old animals by quantitative iTRAQ LC-MS/MS. Protein expression levels of the most interesting candidates were validated by Western Blot analysis. In total, 161 bovine proteins were identified. Of these, 77 molecules were common to the three different age groups, of which 36 defined the NP matrisome. Differential expression levels obtained for Collagen Type XI, XII, XIV, Fibronectin and Prolargin were independently confirmed. Herein, we demonstrate a shift in NP matrisome signatures that occurs in healthy bovine IVDs with development and ageing. Thus, this study provides insight into factors that may explain age-associated IVD degeneration, and which are putative targets for therapy. It also highlights key molecules, characteristic of early developmental stages, which constitute potential effectors in IVD regeneration.
2017-09-25 | PXD004922 | Pride
Project description:The single-cellsequencing of purified wild type rat intervertebral disc (IVD) cells
| PRJNA647600 | ENA
Project description:The pathophysiology of intervertebral disc (IVD) degeneration is not entirely understood; however, environmental and endogenous factors under genetic predisposition are considered to initiate the degenerative changes of human IVDs. Aberrant epigenetic alterations play a pivotal role in several diseases, including osteoarthritis. However, epigenetic alternations, including DNA methylation, in IVD degeneration have not been evaluated. The purpose of this study was to comprehensively compare the genome-wide DNA methylation profiles of human IVD tissues, specifically nucleus pulpous (NP) tissues, with early and advanced stages of disc degeneration. We conducted, for the first time, a genome-wide DNA methylation profile comparative study and observed significant differences in DNA methylation profiles between early and advanced stages of human IVD degeneration. The overview of the DNA methylation profile in the current study revealed that differentially methylated loci were identified in many genes associated with known molecules that have been reported to be relevant to IVD degeneration. Importantly, changes in DNA methylation profiles were also found in genes that regulate the major signaling pathways, such as NF-κB, MAPK, and Wnt signaling, that are well known to be responsible for the pathogenesis of human disc degeneration.
2019-10-01 | GSE129789 | GEO
Project description:Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF-ß superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF-ß has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF-ß action in these specialized joints is not known. One of the hurdles to understanding development of IVD is a lack of known markers. To identify genes that are enriched in the developing IVD and to begin to understand the mechanism of TGF-ß action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in developing vertebrae and IVD. We also compared expression profiles in tissues from wild type and Tgfbr2 mutant mice. Lists of IVD and vertebrae enriched genes were generated. Expression patterns for several genes were verified either through in situ hybridization or literature/ database searches resulting in a list of genes that can be used as markers of IVD. Cluster analysis using genes listed under the Gene Ontology terms multicellular organism development and pattern specification indicated that mutant IVD more closely resembled vertebrae than wild type IVD. We propose TGF-ß has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF-ß that warrant further investigation as regulators of IVD development. Thirteen samples were analyzed. This includes three biological replicates of laser captured IVD from E13.5 day control mice, three biological replicates of laser captured vertebrae from the same E13.5 day control mice, three biological relicates of laser captured vertebrae from E13.5 day Col2aCre;Tgfbr2lox/lox mice, and four biological replicates of laser captured IVD from E13.5 day Col2aCre;Tgfbr2lox/lox mice.
2010-04-09 | E-GEOD-18647 | biostudies-arrayexpress
Project description:Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF-ß superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF-ß has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF-ß action in these specialized joints is not known. One of the hurdles to understanding development of IVD is a lack of known markers. To identify genes that are enriched in the developing IVD and to begin to understand the mechanism of TGF-ß action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in developing vertebrae and IVD. We also compared expression profiles in tissues from wild type and Tgfbr2 mutant mice. Lists of IVD and vertebrae enriched genes were generated. Expression patterns for several genes were verified either through in situ hybridization or literature/ database searches resulting in a list of genes that can be used as markers of IVD. Cluster analysis using genes listed under the Gene Ontology terms multicellular organism development and pattern specification indicated that mutant IVD more closely resembled vertebrae than wild type IVD. We propose TGF-ß has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF-ß that warrant further investigation as regulators of IVD development.
2010-04-09 | GSE18647 | GEO
Project description:To examine the alteration of biological pathways in response to ADAM8-inactivation, an unbiased approach comparing the transcriptome of IVDs in the mutant and WT mice was used.
2024-02-13 | GSE255262 | GEO
Project description:The chronic inflammation resultant from type 2 diabetes (T2D) is also associated with spinal pathologies, including intervertebral disc (IVD) degeneration and chronic neck and back pain. Although confounding factors, such as increased weight gain in obesity, studies have shown that even after adjusting age, body mass index, and genetics (e.g. twins), patients with T2D suffer from disproportionately more IVD degeneration and back pain. We hypothesize that chronic T2D fosters a proinflammatory microenvironment within the IVD that promotes degeneration and disrupts disc homeostasis. To test this hypothesis, we evaluated two commonly used mouse models of T2D – the leptin-receptor deficient mouse (db/db) and the chronic high-fat diet in mice with impaired beta-cell function (STZ-HFD). STZ-HFD IVDs were more degenerated and showed differential expression of chemokines from the db/db models. Moreover, the RNAseq analysis revealed vast transcriptional dysregulation of many pathways in the STZ-HFD but not in the db/db tissues. Taken together, the STZ-HFD may better recapitulates the complexities of the chronic inflammatory processes in the IVD during T2D
2025-03-25 | GSE288503 | GEO
Project description:Using high-precision transcriptomics to systematically map the atlas of human intervertebral disc (IVD) at single-cell resolution. Consequently, we found remarkable cellular diversity in the human IVD and identified a set of signature markers to recognize the cell types spatially. Furthermore, we deciphered a biological classification of chondrocyte subclusters with distinct role in the ECM homeostasis.Notably, the critical clues were also discovered for progenitor cells with bi-lineage differentiation trajectories in the nucleus pulposus, which discriminatively marked by the ancestry molecules PDGFRA and PROCR and highly enriched PDGF network. Finally, we uncovered the potential vital factors maintaining the IVD homeostasis from the intercellular crosstalk based on the signaling network landscape of the IVD microenvironment.
2021-08-20 | GSE160756 | GEO