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SRX13925474: GSM5837333: AB7352; Homo sapiens; RNA-Seq
1 ILLUMINA (NextSeq 500) run: 15.3M spots, 1.3G bases, 524.9Mb downloads

Submitted by: NCBI (GEO)
Study: LGR5 expressing skin fibroblasts define a major hub perturbed in Systemic Sclerosis
show Abstracthide Abstract
Systemic sclerosis (SSc) is an incurable autoimmune disease with high morbidity and mortality rates, with no effective treatment. Here, we conducted a population scale single-cell genomic analysis of skin and blood samples of 56 healthy controls, and 97 SSc patients at different stages of disease. We found immune compartment activation in only a subset of diffuse SSc patients, but global dysregulation of the stromal compartment, including a novel subset of LGR5+ scleroderma associated fibroblasts (ScAF). ScAF cells are mainly localized in the deep reticular dermis of healthy subjects and are dramatically perturbed morphologically and molecularly in SSc patients. Single-cell multiome profiling of the epigenetic and transcriptional landscapes of stromal cells in healthy subjects and SSc patients, revealed ScAF-specific markers, pathways, and transcription factors important in disease development. Systematic analysis combining the clinical metadata and molecular features of the patients, associates specific ScAF targets with disease pathogenesis and SSc clinical traits. Our study provides a high-resolution atlas of the entire spectrum of sclerodermatous skin, proposing a paradigm shift in the understanding of SSc disease and facilitating the development of new biomarkers and therapeutic strategies for SSc. Overall design: Patients who were diagnosed with SSc based on the 2013 American College of Rheumatology/European League against Rheumatism revised criteria for SSc (Van Den Hoogen et al., 2013), were recruited to the study from rheumatology departments in two medical centers in Israel. We excluded SSc patients under biological Disease-Modifying antirheumatic Drugs (DMARDs). After informed consent (in accordance with Helsinki declaration), skin samples were obtained through punch biopsy (4 mm), 10 cm distal to the elbow and placed in saline containing tubes on ice and then transferred to cold FACS buffer (EDTA pH8.0 2mM, BSA 0.5% in PBS). Whole blood samples were collected at the time of skin biopsy, were placed in EDTA-containing tubes (Beckton Dickenson) on ice and diluted 1:1 with ice cold FACS buffer. Skin and blood samples immediately transported to the lab. As a control, we also collected blood and skin samples from healthy patients following the same procedure.
Sample: AB7352
SAMN25279411 • SRS11774007 • All experiments • All runs
Organism: Homo sapiens
Library:
Instrument: NextSeq 500
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: human sample collection: skin samples were obtained through punch biopsy (4 mm), 10 cm distal to the elbow and placed in saline containing tubes on ice and then transferred to cold FACS buffer (EDTA pH8.0 2mM, BSA 0.5% in PBS). Whole blood samples were collected at the time of skin biopsy, were placed in EDTA-containing tubes (Beckton Dickenson) on ice and diluted 1:1 with ice cold FACS buffer. Skin and blood samples immediately transported to the lab. Skin cell suspension and blood mononuclear cells were stained with the following antibodies: CD45 (PerCp/Cyanine, 3040285.5, Biolegend), CD90 (PE 328144, Biolegend), LGR5 (PE, 373803, Biolegend), CD55 (FITC, 311306, Biolegend). All FACS antibodies were used with a 1:100 dilution. Samples were filtered through a 40μm strainer before commencing sorting. Single cell sorting was performed using FACSAria Fusion cell sorter (BD Biosciences, San Jose, CA). After doublets exclusion, isolated live cells were single-cell sorted into 384-well cell capture plates containing 2μL of lysis solution and barcoded poly(T) reverse-transcription (RT) primers for single-cell RNA-seq. Four empty wells were kept in each 384-well plate as a no-cell control for data analysis. Immediately after sorting, each plate was spun down to ensure cell immersion into the lysis solution, snap frozen on dry ice, and stored at –80°C until processed. Cells were analyzed using BD FACSDiva software (BD Bioscience) and FlowJo software (FlowJo, LLC). Single-cell RNA-seq libraries were prepared as previously described {Jaitin, 2014}. In brief, mRNA from single cells sorted into capture plates were barcoded and converted into cDNA and then pooled using an automated pipeline. The pooled sample was linearly amplified by T7 in vitro transcription, and the resulting RNA was fragmented and converted into a sequencing-ready library by tagging the samples with pool barcodes and Illumina sequences during ligation, RT, and PCR. Each pool of cells was tested for library quality and concentration as described previously {Jaitin, 2014}
Experiment attributes:
GEO Accession: GSM5837333
Links:
Runs: 1 run, 15.3M spots, 1.3G bases, 524.9Mb
Run# of Spots# of BasesSizePublished
SRR1776292415,257,2341.3G524.9Mb2022-04-06

ID:
19415018

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