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Genetic Signatures from RNA sequencing of Pediatric Localized Scleroderma (LS) Skin

ABSTRACT: Genetic Signatures from RNA sequencing of Pediatric Localized Scleroderma (LS) Skin

PROVIDER: PRJNA702138 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13723048_1.fastq.gz	Fastqsanger.gz
	SRR13723048_2.fastq.gz	Fastqsanger.gz
	SRR13723049_1.fastq.gz	Fastqsanger.gz
	SRR13723049_2.fastq.gz	Fastqsanger.gz
	SRR13723050_1.fastq.gz	Fastqsanger.gz

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Genetic Signatures from RNA sequencing of Pediatric Localized Scleroderma (LS) Skin

Project description:In this study, we explored the initial results of RNA transcriptomic expression between pediatric localized scleroderma skin tissue and healthy control skin, with a subanalyses of transcriptomic expression in different disease states. LS gene signatures compared to healthy controls showed a distinct expression of an inflammatory response gene signature (IRGS) composed of IFNγ, IFNα and TNFα associated genes.

2021-06-12 | GSE166861 | GEO

Transcriptomic evaluation of pediatric localized scleroderma skin with histological and clinical correlation

Project description:In this study, we explored enhanced results of RNA transcriptomic expression between pediatric localized scleroderma skin tissue and healthy control skin. Additional histological and clinical comparison of LS patient features with DEGs supports an inflammatory and fibroproliferative grouping demonstrated in unsupervised clustering of the transcriptomic data.

2021-06-12 | GSE166863 | GEO

Transcriptomic evaluation of pediatric localized scleroderma skin with histological and clinical correlation

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DNA methylation patterns in juvenile systemic sclerosis and localized scleroderma

Project description:Scleroderma refers to a group of chronic fibrotic immune-mediated diseases of unknown etiology. Characterizing epigenetic changes in childhood-onset scleroderma, systemic sclerosis or localized scleroderma, has not been previously performed. The aim of this study was to assess DNA methylation differences and similarities between juvenile systemic sclerosis (jSSc) and juvenile localized scleroderma (jLS) compared to matched healthy controls. Genome-wide DNA methylation changes in peripheral blood mononuclear cell samples were assessed using the MethylationEPIC array followed by bioinformatic analysis and limited functional assessment. We identified a total of 105 and 144 differentially methylated sites compared to healthy controls in jSSc and jLS, respectively. The majority of differentially methylated sites and genes represented were unique to either jSSc or jLS suggesting a different underlying epigenetic pattern in both diseases. Among shared differentially methylated genes, methylation levels in a CpG site in FGFR2 can distinguish between LS and healthy PBMCs with a high accuracy. Canonical pathway analysis revealed that inflammatory pathways were enriched in genes differentially methylated in jSSc, including STAT3, NF-κB, and IL-15 pathways. In contrast, the HIPPO signaling pathway was enriched in jLS. Our data also suggest a potential role for NOTCH3 in both jSSc and jLS, and revealed a number of transcription factors unique to each of the two diseases. In summary, our data revealed important insights into jSSc and jLS and suggest a potentially novel epigenetic diagnostic biomarker for LS.

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Genetic Signatures From RNA Sequencing of Pediatric Localized Scleroderma Skin.

Project description:The purpose of this study was to explore the skin transcriptional profile in pediatric localized scleroderma (LS) to provide a better understanding of the altered immune and fibrotic pathways promoting disease. LS is a progressive disease of the skin and underlying tissue that causes significant functional disability and disfigurement, especially in developing children. RNA sequencing (RNAseq) technology allows for improved understanding of relevant cellular expression through transcriptome analysis of phases during LS disease progression (more active/inflammatory vs. inactive/fibrotic) and also permits the use of RNA extracted from existing paraffin-embedded skin tissue, which is important in pediatrics. A strong correlation was observed between the comparison of genes expressed between fresh (RNAlater) and paraffinized skin in healthy and LS subjects, supporting the use of paraffinized tissue. LS gene signatures compared to healthy controls showed a distinct expression of an inflammatory response gene signature (IRGS) composed of IFNγ-, IFNα-, and TNFα-associated genes. GSEA© enrichment analysis showed that the IRGS, including interferon-inducible chemokines such as CXCL9, CXCL10, CXCL11, and IFNγ itself, was more highly expressed in LS patients with more inflammatory lesions. The use of paraffinized skin for sequencing was proven to be an effective substitute for fresh skin by comparing gene expression profiles. The prevalence of the IFNγ signature in the lesion biopsies of active LS patients indicates that these genes reflect clinical activity parameters and may be the promoters of early, inflammatory disease.

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Project description:Localized scleroderma (LoS), or morphea, refers to a group of rare autoimmune connective tissue diseases. Autologous fat grafting was able to correct volume loss in patients with LoS to improve facial disfigurement.However, whether it could exert a positive effect on reversing skin sclerosis remains unclear.

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