Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Shared and compartment-specific processes in nucleus pulposus and annulus fibrosus during intervertebral disc degeneration

ABSTRACT: Elucidating how cell populations promote onset and progression of intervertebral disc degeneration (IDD) has the potential to enable more precise therapeutic targeting of cells and mechanisms. Single cell RNA-sequencing (scRNA-seq) was performed on surgically separated annulus fibrosus (AF) (19,978; 26,983 cells) and nucleus pulposus (NP) (20,884; 24,489 cells) from healthy and diseased human intervertebral discs (IVD). In both tissue types, we observed depletion of cell subsets involved in maintenance of healthy IVD, specifically the immature cell subsets – fibroblast progenitors and stem cells – indicative of an impairment of normal tissue self-renewal. We also identified tissue-specific changes. In NP, several fibrotic populations were increased in degenerated IVD, indicating tissue-remodeling. In degenerated AF, we identified a novel disease-associated subset, which is a stem cell-derived abnormally differentiated chondrocytic population and expresses disease-promoting genes. It was associated with pathogenic biological processes and the main gene regulatory networks includedthrombospondinsignaling and FOXO1 transcription factor. Our data reveal new insights of both shared and tissue-specific changes in specific cell populations in AF and NP during IVD degeneration. These identified mechanisms and molecules are novel and more precise targets for IDD prevention and treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE230808 | GEO | 2024/04/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of bovine nucleus pulposus, carticular cartilage and annulus fibrosus cells to further determine expression in normal and degenerate human intervertebral disc

Project description:The aim of this transcription profiling study was to identify novel genes that could be used to distinguish bovine Nucleus pulposus (NP) cells from articular cartilage (AC) and annulus fibrosus (AF) cells and to further determine their expression in normal and degenerate human intervertebral disc (IVD). This study has identified a number of novel genes that characterise the bovine and human NP and IVD cell phenotypes and allows for discrimination between AC, AF and NP cells.<br><br>

2010-03-05 | E-MEXP-2291 | biostudies-arrayexpress

Nucleus pulposus related lncRNA and mRNA expression profiles in intervertebral disc degeneration

Project description:Intervertebral disc degeneration (IDD) leads to low back pain and disability globally. The pathophysiology of IDD is not entirely understood. There is increasing evidence that long noncoding RNAs (lncRNAs) play a key regulatory role in a wide range of biological processes. The purpose of this study was to comprehensively lncRNA and mRNA expression profiles of human intervertebral disc (IVD) tissues, specifically nucleus pulpous (NP) tissues, with early and advanced stages of disc degeneration. The overview of lncRNA and mRNA expression profiles in the current study revealed that differentially expressed lncRNAs and mRNAs were identified that have been reported to be relevant to IDD. Importantly, differentially expressed lncRNAs and mRNAs 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 IDD.

2023-02-09 | GSE186542 | GEO

Actively synthesised proteins in human intervertebral disc

Project description:The intervertebral disc (IVD) is a joint in the spine that facilitates daily movement, comprising of the central nucleus pulposus (NP), surrounded by the annulus fibrosus (AF) and sandwiched between two cartilage endplates that function together as a unit. Changes to the IVD occur with aging, most drastically in the NP where it experiences dehydration and loss of cellularity, directly impacting on the integrity of the biomechanical functions of the IVD. Whilst the static proteome reflects the long-term accumulation of proteins and their turnover over the lifetime of the IVD, this information may not reflect immediate cellular changes that may alter during the course of time. To gain a better understanding of cellular function and protein turnover in disc homeostasis (health) versus aging, we analysed the actively synthesized proteins using the SILAC approach. Clinical specimens from spine surgeries for scoliosis (young samples; NP n=2, AF n=4) or degeneration (aged samples; NP n=1, AF n=1) were used in this study.

2021-01-29 | PXD018193 | Pride

In vitro differentiation of pluripotent stem cells towards notochordal-like cells

Project description:Description: The intervertebral disc (IVD) is a joint in the spine that is comprised of three major structures, the nucleus pulposus (NP), annulus fibrosus (AF) and cartilaginous endplate (EP). The NP is a proteoglycan-rich structure which contains a heterogenous population including the presence of progenitors such as the notochordal-like cells (NLCs) and NP cells, which are responsible for the synthesis and turnover of extracellular matrix in the NP. During aging and degeneration, there is a loss of cells, hydration, and changes in the ECM, that leads to the alterations in the biomechanical function of the IVD. The replenishment of cells, in particular, the progenitors are a potential therapy for IVD degeneration. However, a major challenge lies in obtaining sufficient numbers of healthy cells for treatment. This study used a 3 part protocol to differentiate pluripotent stem cells into NLCs in vitro.

2023-11-11 | GSE237546 | GEO

Proteomic landscape of murine intervertebral disc reveals mechanisms involved in homeostasis and disc structure maintenance

Project description:To fully apprehend the complex mechanisms responsible for intervertebral disc (IVD) degeneration, one needs to gain a deeper understanding of what characterizes a healthy disc. Using a quantitative proteomic approach, we analyzed methodically the differences existing between IVD genders, levels and components. A total of 2776 proteins were identified and we showed that cross regional but not gender variation existed along the mouse spine. Components comparison established CD109, CD81 and Col12a1 as novel NP and AF markers. NP cell clustering involved Cdh2 and tight junctions whereas early phase of adaptation to hypertonicity, the regulation of cell volume, was ensured by Slc12a2 and Wnk1. AF cells were protected from oxidative stress by expressing Atox1 and Sod3. Finally notochordal-like cells vacuoles were not acidic nor lipid droplets. Altogether, our study provides a first comprehensive landscape of the biology of a healthy murine IVD and identifies mechanisms involved in homeostasis and structure maintenance.

2021-09-07 | PXD006671 | Pride

stseranidou2024 - Nucleus Pulposus Cell Network Modelling in the Intervertebral Disc

Project description:ABSTRACT: Intervertebral disc degeneration (IDD) arises from an intricate imbalance between the anabolic and catabolic processes governing the extracellular matrix (ECM) within the disc. Biochemical processes are complex, redundant and feedback-looped, and improved integration of knowledge is needed. To addess this, a literature-based regulatory network model (RNM) for nucleus pulposus cells (NPC) is proposed, representing the normal state of the intervertebral disc (IVD), in which proteins are represented by nodes that interact among each other through activation and/or inhibition edges. This model includes 32 different proteins and 150 edges by incorporating critical biochemical interactions in IVD regulation, tested in vivo or vitro in humans’ and animals’ NPC, alongside non tissue specific protein-protein interactions. We used the network to calculate the dynamic regulation of each node through a semi-quantitative method. The basal steady state successfully represented the activity of a normal NPC, and the model was assessed through the published literature, by replicating two independent experimental studies in human normal NPC. Pro-catabolic or pro-anabolic shifts of the network activated by nodal perturbations could be predicted. Sensitivity analysis underscores the significant influence of transforming growth factor beta (TGF-β) and interleukin-1 receptor antagonist (IL-1Ra) on the regulation of structural proteins and degrading enzymes within the system. Given the ongoing challenge of elucidating the mechanisms driving ECM degradation in IDD, this unique IVD RNM holds promise as a tool for exploring and predicting IDD progression, shedding light on IVD phenotypes and guiding experimental research efforts.

2024-11-04 | MODEL2407080001 | BioModels

Gene expression data for human intervertebral discs

Project description:The human intervertebral disc (IVD) is a complex and dynamic structure that functions to provide spinal stability, mobility and flexibility. It comprises three main compartments: 1) a water-rich central compartment called the nucleus pulposus (NP), which is enveloped by 2) the annulus fibrosus (AF) and sandwiched between 3) two cartilaginous endplates (EP) from which the IVD gains its nutrition and provides a means to get rid of metabolic waste. The IVD is constantly under extreme conditions of hypoxia, nutrition, and loading stresses. As such, it wears with ageing, and the rates of wearing may be sped up by a multitude of risk factors. Phenotypically, the AF may become weaker that a portion of it may protrude into neighboring tissues, resulting in disc bulging, or even worse, it may rupture and form a herniation Most striking of all, magnetic nuclear imaging (MRI) of the NP may become darker, with spotted high-intensity zones (HIZs), indications of dehydration and annular disruptions (Peng, et al. 2006). In a herniated or even collapsed disc, the contents of NP may leak into the neighboring spaces and external cells (such as macrophages) may infiltrate into the NP (Nakazawa, et al. 2018), causing the disc functions to be partially or fully compromised. The underlying mechanism of these involves complex interplays of cellular and molecular changes and remains poorly understood; nevertheless, the process is suggested to be triggered and driven by both environmental and genetic factors, or their combinations. In an effort to study the molecular dynamics of the ageing process of the human IVD, we profiled the transcriptomes of two groups of individuals: a young and non-degenerated group (N=2) and an aged and degenerated group (N=2). We profiled the transcriptomes of both AF and NP for each individual.

2020-06-30 | GSE147383 | GEO

Dynamics of N6-methyladenosine modification during aging and their potential roles in the degeneration of intervertebral disc

Project description:N6-methyladenosine (m6A) modification, as one of the epigenetic modification of mRNAs, has been found implicating in various musculoskeletal disorders including IDD. However, the m6A dynamics in the progression of aging related IDD remain largely unknown. The purpose of this study was to investigate the m6A methylome of nucleus pulpous (NP) tissues from intervertebral disc (IVD) at different ages of rats.

2023-06-15 | GSE234369 | GEO

Single-cell RNA-seq analysis of cells from degenerating and non-degenerating intervertebral discs from the same individual reveals new biomarkers for intervertebral disc degeneration

Project description:Low back pain continues to be a major public health problem worldwide. In this study, we used single-cell transcriptomic analysis to identify new specific biomarkers for nucleus pulposus (NP) and annulus fibrosis (AF) cells and to define cell populations within non-degenerating and degenerating human intervertebral discs (IVD). Freshly isolated human NP and AF cells were separately isolated from non-degenerating (nD) and degenerating (D) discs of the same individual. Isolated cells were subjected to droplet-based single-cell RNA sequencing (scRNA-Seq) using 10X Genomics platform. A total of 3134 (AFD), 3182 (AFnD), 3665 (NPD) and 3918 (NPnD) individual cells were profiled from nD and D discs respectively.

2022-03-31 | GSE199866 | GEO

The degradome of the human intervertebral disc

Project description:The intervertebral disc (IVD) is a joint in the spine that facilitates daily physical activity, comprising of the central nucleus pulposus (NP), surrounded by the annulus fibrosus (AF) and sandwiched between two cartilage endplates that function together as a unit. Changes to the IVD occur with aging, most drastically in the NP where it experiences dehydration and loss of cellularity, directly impacting on the integrity of the biomechanical functions of the IVD. We were interested in examining the types of degraded proteins in young and aged disc samples to further understand the protein turnover in aging and homeostasis. We analysed the degradome for degraded proteins using terminal amine isotopic labeling of substrates (TAILS) Clinical specimens from spine surgeries for scoliosis (young samples, n=3) or degeneration (aged samples, n=3) were used in this study.

2021-01-29 | PXD018298 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data