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Single-cell RNA sequencing reveals the CRTAC1+ population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1+ macrophage

ABSTRACT: Single-cell RNA sequencing reveals the CRTAC1+ population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1+ macrophage

PROVIDER: PRJNA1129430 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29637200.fastq.gz	Fastqsanger.gz
	SRR29637201.fastq.gz	Fastqsanger.gz
	SRR29637202.fastq.gz	Fastqsanger.gz
	SRR29637203.fastq.gz	Fastqsanger.gz
	SRR29637204.fastq.gz	Fastqsanger.gz

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Single-cell RNA sequencing reveals the CRTAC1+ population actively contributes to the pathogenesis of spinal ligament degeneration by SPP1+ macrophage

Project description:Degenerative spinal stenosis is a chronic disease that affects the spinal ligaments and associated bones, resulting in back pain and disorders of the limbs among the elderly population. There are few preventive strategies for such ligament degeneration. We here aimed to establish a comprehensive transcriptomic atlas of ligament tissues to identify high-priority targets for pharmaceutical treatment of ligament degeneration. Here, single-cell RNA sequencing was performed on six degenerative ligaments and three traumatic ligaments to understand tissue heterogeneity.

2024-07-31 | GSE271018 | GEO

Microglia-RPE Cell Communication via the SPP1-ITGAV Axis Drives EMT and Retinal Degeneration in Dry AMD

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Experimental study on gene expression profile of medial meniscus after resection of anterior cruciate ligament and lateral collateral ligament

Project description:To explore the molecular mechanisms of meniscal degeneration after resection of anterior cruciate ligament and lateral collateral ligament, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential role in the development of meniscal degeneration. The anterior cruciate ligament (ACL) and lateral collateral ligament (LCL) of the right rear limbs of Wuzhishan minipig was resected at the same time, and the left rear limbs was sham operated. There were significant differences in gene expression between the two groups. A total of 893 differentially expressed genes were identified, of which 537 were upregulated and 356 were downregulated. This study indicated that several molecular mechanisms were implicated in the development of meniscal degeneration, thus improving our understanding of meniscal degeneration and offering molecular targets for future therapeutic advances.

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RNA-seq in chondrocyte differentiation of human spinal ligament cells

Project description:Ectopic endochondral ossification in the tendon/ligament is caused by repetitive mechanical overload or inflammation. Tendon stem/progenitor cells (TSPCs) contribute to tissue repair and lubrication by producing proteoglycan 4 (Prg4). However, the mechanisms of ectopic ossification and association of TSPCs are not yet known. Here, we investigated the characteristics of Prg4-positive (+) cells and identified that R-spondin 2 (RSPO2), a WNT activator, is specifically expressed in a distinct Prg4+ TSPC cluster. The Rspo2+ cluster was characterized as mostly undifferentiated, and RSPO2 overexpression suppressed ectopic ossification in a mouse Achilles tendon puncture model via chondrogenic differentiation suppression. RSPO2 expression levels in patients with ossification of the posterior longitudinal ligament were lower than those in spondylosis patients, and RSPO2 protein suppressed chondrogenic differentiation of human ligament cells. RSPO2 was induced by inflammatory stimulation and mechanical loading via nuclear factor-kappa B (NF-κB). Rspo2+ cells may contribute to tendon/ligament homeostasis by suppressing chondrogenic differentiation.

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Effect of Cyclic stretching on the gene expression in human spinal ligament cells

Project description:Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by progressive ectopic bone formation in the spinal ligament. To identify the genes related to ectopic ossification of human spinal ligament affected by mechanical stress, analyses using cDNA microarray were carried out using cultured human spinal ligament cells that had been subjected to uniaxial cyclic stretching. cDNA microarrays revealed that ranges of distribution of both up- and down-regulated genes evoked by cyclic stretching were significantly wider in cells from than in non-OPLL cells. Keywords: mechanical-stress response

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Altered extracellular matrix protein dynamics distinguishes canine ligament-derived stem cells from fibroblasts

Project description:Ligaments are prone to injury and degeneration in humans and animals, however the healing potential of ligament is poor and current treatment options lack effectiveness. Stem cell-based therapies hold potential for treatment of ligament injuries. This study aimed to characterise ligament-derived stem cell (LDSC) and ligament fibroblast populations as well as to identify specific niche components which could be used to promote the survival and function of LDSCs. LDSCs and ligament fibroblasts were isolated from canine cranial cruciate ligament and characterised for clonogenicity, multipotency and marker expression. The extracellular matrix (ECM) composition was characterised using a novel metabolic labelling and mass spectrometry approach. Both cell types demonstrated clonogenicity, with significant differences seen in colony size. Stem cell and tenogenic marker expression was increased in LDSCs compared with ligament fibroblasts, although this was only significant for the MSC marker CD73. Both cell types demonstrated multipotency, however this was more marked in LDSCs. A number of collagens, glycoproteins, proteoglycans and ECM regulators were identified in both the LDSC and ligament fibroblast niche using proteomics, with some differences between cell types, including collagens, decorin and fibronectin. Metabolic labelling of cells demonstrated unique turnover profiles for distinct ECM protein groups, with significant differences in new synthesis seen between cell types for a number of proteins, including collagen, decorin and elastin. In conclusion, different cell populations were observed in canine ligament with differences in niche composition and dynamics seen between the two cell types. These differences could be exploited to aid identification of LDSCs and to promote survival and function of LDSCs for potential therapeutic strategies.

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Project description:Histone H3K4 methylation is a feature of meiotic recombination hotspots shared by many organisms including plants and mammals. Meiotic recombination is initiated by programmed double strand break (DSB) formation that in budding yeast is directed in gene promoters by histone H3K4 di/trimethylation. This histone modification is indeed recognized by Spp1, a PHD-finger containing protein that belongs to the conserved histone H3K4 methyltransferase Set1 complex. During meiosis, Spp1 binds H3K4me and recruits a DSB protein, Mer2, to promote DSB formation close to gene promoters. How Set1C and Mer2 related functions of Spp1 are connected is not clear.

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New protein from an unexpected ligament

Project description:This study describes the discovery of the gene responsible for differentiation of stem cells into ligament tissue. This important finding may lead to the development of treatments for gonarthrosis, rupture of the cruciate ligament and periodontal ligament, and ossification of the posterior longitudinal ligament. This study describes the discovery of the gene (A) responsible for differentiation of stem cells into ligament tissue. The transfection of this gene into mouse mesenchymal stem cells resulted in the formation of ligament-like connective tissue composed of parallel fibres. We performed microarray analysis of four samples: stem cells (sample1), ligament-like tissue from stem cells transfected with A (sample 4), ligament tissue from A-transgenic mice (sample 2) , and ligament tissue from wild type mice (sample 3).

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Expression data from human periodontal ligament

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