Glis1 and oxaloacetate in nucleus pulposus stromal cell somatic reprogramming and survival
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ABSTRACT:
ORGANISM(S): Bos taurus
PROVIDER: GSE216377 | GEO | 2022/10/28
REPOSITORIES: GEO
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Project description:The aim of this study was threefold: Firstly, to carry out microarray hybridisations using human AC and NP cells to identify NP and AC specific markers. Secondly, to further investigate their ability to characterise adult derived stem cells differentiating towards an NP phenotype using an in vitro differentiation system and thirdly, in their application to compare the suitability of BMSC and ADRCs as a stem cell source for tissue engineering of the IVD. Using microarray technology we have identified several novel human AC and NP markers and have demonstrated that these markers are capable of identifying the differentiation of adult derived stem cells towards an NP rather than an AC phenotype. In addition these markers suggest that ADRCs provide a more suitable cell source for tissue engineering of the intervertebral disc.
2010-12-01 | E-MEXP-2488 | biostudies-arrayexpress
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
Project description: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.
2024-04-05 | GSE230808 | GEO
Project description:Failure of the nucleus pulposus (NP) causes intervertebral disc (IVD) disease and associated low-back pain, which are highly prevalent among the aged populations. Molecular and cellular changes underpinning the structural failures in age-associated IVD diseases (IDDs) remain poorly elucidated. Here, we first identified that TAGLN, which encodes the cytoskeleton regulator transgelin, was transcribed in healthy NPs of both human and mouse, but diminished with ageing. Immunostaining showed that TAGLN were expressed on the peripheral of mouse NP (periNP). Lineage analyses in Tagln-CreERT2 mice showed that NP cells were derived from Tagln+ cells in the periNP. The PeriNP cells were proliferative and can differentiate into the inner NP (innerNP). These Tagln+ cells and their descendants diminish with ageing or puncture-induced degeneration. Single-cell transcriptomics from neonatal and adult Tagln-CreERT2 IVDs confirmed that Tagln descendants uniquely populate the NP, wherein four sub-populations were identified: chondrocyte-like, Cd228+, Tagln+ and Car3+. Immunostaining confirmed Car3 expressed in innerNP. Computational analysis indicated the lineage trajectory from Tagln+ to Car3+ sub-population, along with the involvement of Fos/Jun/TGFβ cascades and partial epithelial-to-mesenchymal transition process. Removal of TGFβ mediator Smad4 by notochord specific Foxa2mNE-Cre resulted in decreased Tagln+ cells and abnormal disc morphology, resembling disc degeneration. Our study generates a single-cell transcriptomic atlas for healthy IVD, identifies Tagln+ PeriNP cells as a progenitor pool crucial for the IVD homeostasis, and provides potential targets for regenerative cell therapy against IVD degeneration.
2024-05-14 | GSE201396 | GEO
Project description:Given the leading cause of disability worldwide, low back pain (LBP) is recognized as a pivotal socio-economic challenge to the aging population, which is importantly attributed to intervertebral disc degeneration (IVDD), a highly prevalent affliction of aging. Elastic nucleus pulposus (NP) tissue is essential for maintenance of IVD structural and functional integrity. Native NP cells exhibit crucial functions for regulating extracellular matrix homeostasis, constructing an accommodating biomechanical environment and maintaining the gelatinous property of NP tissue. The accumulation of senescent NP cells with inflammatory hypersecretory phenotype due to aging and other damaged factors is a distinctive hallmark of IVDD initiation and progression. In this study, we revealed a mechanism of IVDD progression in which aberrant genomic DNA damage promotes NP cell inflammatory senescence via activation of cGAS-STING axis. cGAS-STING axis activation drove inflammatory phenotype acquisition and inflammatory hypersensitivity to damaged signals of senescent NP cells via p65-mediated transcriptional modulation. And STING pharmacological inhibitor notably suppressed p65-mediated inflammatory response formation and senescence-associated screctory phenotype (SASP) acquisition of senescent cells.
2024-03-20 | GSE244403 | GEO
Project description:Induced pluripotent stem cells (iPSC) are generated from somatic cells by the transgene expression of three transcription factors Oct3/4, Sox2, and Klf4 (OSK), albeit at a low efficiency. The protooncogene c-Myc enhances the efficiency of iPSC generation by OSK, but it also increases the tumorigenicity of the resulting iPSC. In the current study, we found the Gli-like transcription factor Glis1, when expressed together with OSK, to markedly enhance the generation of iPSC from both mouse and human fibroblasts. Mouse iPSC generated by OSK and Glis1 can form germline-competent chimeras. Glis1 is enriched in unfertilized oocytes and one cell-stage embryos. DNA microarray analyses revealed that Glis1 promotes multiple pro-reprogramming pathways, including Myc, Nanog, Lin28, Wnt, mesenchymal-epithelial transition (MET), and Esrrb. These results therefore demonstrated that oocyte transcription factor Glis1 effectively promote direct reprogramming during iPSC generation. p53-null mouse embryonic fibroblasts were transduced with OSK and OSK+Glis1 and were used for microarray analyses.
2011-06-10 | E-GEOD-26429 | biostudies-arrayexpress
Project description:Purpose: Degeneration and aging of the nucleus pulposus (NP) of the intervertebral disc (IVD) is accompanied by alterations in NP cell phenotype marked by reduced cellularity and a shift towards a fibroblast-like state. We have recently demonstrated an ability to manipulate the phenotypic expression of adult degenerative NP cells by culture upon poly(ethylene glycol) (PEG) based hydrogels dually functionalized with integrin- and syndecan-binding laminin-mimetic peptides. In the present study, we seek to understand the transcriptome changes elicited by NP cell interactions with the presented hydrogel system. Methods: mRNA profiles of NP from 3 human tissue samples were cultured for 4 days on either tissue culture polysyrene (TCPS) or the functionalized gel before RNA was isolated and sequenced, 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 (gel/TCPS) that was greater than or equal to 2 or less than or equal to negative 2 and a p-value of less than or equal to 0.05. Results: The data corroborate and expand on the previous findings by demonstrating that degenerative adult human NP cells cultured upon these gels have upregulations in some markers of NP and notochordal cells but also downregulations of some NP-specific markers and several fibroblastic markers. Furthermore, through gene set enrichment analysis we have shown that pathways related to cell differentiation and notochord morphogenesis were upregulated in the gel condition. Additionally, 13 genes associated with G protein-coupled receptors, many of which are known drug targets, were identified as up or downregulated following periods of culture upon the gel condition. Conclusions: The data from this RNA-sequencing demonstrate that culture on laminin-mimetic-peptide presenting gels can modulate cell phenotype and promotes upregulation of NP and notochordal markers.
2021-02-01 | GSE154044 | GEO
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
Project description:Intervertebral Disc (IVD) degeneration leading to Low back pain (LBP) is the most common musculoskeletal disorder. Lack of knowledge on the intricate homeostatic mechanisms necessitates proteomic characterisation of a normal human IVD to understand the biological process and unravel the pathomechanisms of degenerative disc disease (DDD). In this study, we employed proteomic approach coupled with tandem mass-spectrometry to derive the comprehensive list of proteins expressed in true biologically normal control discs. This would serve as the basis for identifying the interacting molecules participating in significant biological processes and pathways disrupted during aging and degeneration.
2021-09-09 | PXD016560 | Pride
Project description:To evaluate the effect of Hypoxia-inducible factor 1-alpha inhibitor (HIF-1) in nucleus pulposus (NP) cells, human NP cells were lentivirally transduced with either control or FIH-1 targeted shRNA. Gene expression changes between samples from control and FIH-1 silenced cells were evaluated using a microarray. Primary NP cells were isolated from human discs and grown in culture. Cells were transduced with either control or FIH-1 targeting shRNA constructs. Silencing of FIH-1 was confirmed for each set using qRT-PCR and Western blot. Total RNA from NP cells was used for RNA extraction and hybridization on the Affymetrix microarray. Control samples: C1, C2, and C3 and FIH-1-silenced samples: E1, E2, and E3.
2014-05-27 | E-GEOD-55844 | biostudies-arrayexpress