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:Regenerative medicine aims to repair degenerate tissue through cell refurbishment with minimally invasive procedures. Adipose tissue (FAT)-derived stem or stromal cells are a convenient autologous choice for many regenerative cell therapy approaches. The intervertebral disc (IVD) is a suitable target. Comprised of an inner nucleus pulposus (NP) and an outer annulus fibrosus (AF), the degeneration of the IVD through trauma or aging presents a substantial socio-economic burden worldwide. The avascular nature of the mature NP forces cells to reside in a unique environment with increased lactate levels, conditions that pose a challenge to cell-based therapies. We assessed adipose and IVD tissue-derived stromal cells through in vitro transcriptome analysis in 2D and 3D culture and suggested that the transcription factor Glis1 and metabolite oxaloacetic acid (OAA) could provide NP cells with survival tools for the harsh niche conditions in the IVD.
| S-EPMC9671658 | biostudies-literature
Project description:Glis1 and oxaloacetate in nucleus pulposus stromal cell somatic reprogramming and survival
| PRJNA893367 | ENA
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:The physiological function of the intervertebral disc (IVD) depends on the cellular and molecular composition of the nucleus pulposus (NP), which plays a key role in managing the mechanical loading of the IVD.We conducted single-cell RNA sequencing (scRNA-seq) analysis to better characterize the NP cells, particularly the Shh-tdTom+ NP cells, in the adult Shh-CreER; Rosa26tdTomato mice.
2025-02-15 | GSE255488 | GEO
Project description:Nucleus pulposus (NP) resides in hypoxic microenvironment due to the avascular structure of intervertebral disc (IVD). Intracellular lactate drives lysine lactylation (Kla) as a newly epigenetic modification. However, the impact of Kla on NPCs remains unknown. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we showed a global lactylome profiling on NPCs cultured in normoxia and hypoxia environment and found that 3510 lactylation sites on 1052 proteins in NPCs on non-histone proteins. Moreover, there are 18 proteins with 129 Kla sites exclusively detected in the normoxia group, and 117 Kla sites in 27 proteins were specific in hypoxia group. Together, our dates reveals that Kla plays an important role in regulating cellular metabolism and may contribute to IDD progression.
2025-05-06 | PXD048244 | Pride
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