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Series GSE246562 Query DataSets for GSE246562
Status Public on Nov 02, 2023
Title Effects of ECM rigidity on normal and keloid dermal fibroblasts
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary This study investigated the effects of extracellular matrix (ECM) rigidty on gene expression patterns in normal dermal fibroblasts (NDFs) and keloid dermal fibroblasts (KDFs). Cells were cultured on collagen coated polyacrylamide hydrogels with elastic moduli mimicking normal skin (8 kPa) or keloid scar tissue (214 kPa), and changes in gene expression were profiled using next-generation RNA-sequencing. Differential gene expression analysis identified overall significant differences in gene expression between the NDF and KDF populations. Despite high levels of inter-patient heterogeneity in the KDF samples, further principal components analysis revealed a subset of genes (PC5) that were specifically regulated by ECM rigidity. Gene set enrichment analysis of the PC5 genes identified classic pathways associated with mechanotransduction, including Hippo Signalling and Regulation of the Actin Cytoskeleton, as well as genes associated with the Autophagy pathway. Additional in vitro studies and human tissue staining confirmed the biomechanical regulation of autophagic flux in NDFs and KDFs and differential remodelling of the lysosome in KDFs and keloid scars. Together, these findings implicate autophagy and lysosomal remodelling as biomechanically dysregulated pathways in keloid fibroblasts, and these mechanisms may contribute to scar pathogenesis.
 
Overall design NDFs and KDFs from three different donors were cultured on polyacrylamide gels coated with type I collagen for 24 hours. Total RNA was isolated for each sample and sequenced using the Illumina NextSeq platform. Subsequent differential gene expression and pathway analysis was performed using the SeqMonk and Webgestalt platforms
 
Contributor(s) Connelly J, Ross R
Citation(s) 38763173
Submission date Oct 30, 2023
Last update date May 24, 2024
Contact name John Connelly
E-mail(s) j.connelly@qmul.ac.uk
Organization name Queen Mary University of London
Department Blizard Institute
Street address 4 Newark Street
City London
State/province London
ZIP/Postal code E1 2AT
Country United Kingdom
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (12)
GSM7871595 NDF donor 1, 8kPa
GSM7871596 NDF donor 1, 214kPa
GSM7871597 NDF donor 2, 8kPa
Relations
BioProject PRJNA1033633

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Supplementary file Size Download File type/resource
GSE246562_All_Probes_Raw_counts.csv.gz 1.2 Mb (ftp)(http) CSV
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Raw data are available in SRA

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