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Comparative analysis of chromatin accessibility during chondrogenesis and in osteoarthritis

GSE270602 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 26 samples Submitted 2025/01/01 Platform GPL24676
Summary
To reveal the organisation of the cartilage cell chondrocyte genome and identify changes that occur within this organisation during development and due to osteoarthritis (OA). Methods Assay for Transposase -Accessible Chromatin using Sequencing (ATAC-seq) was performed on chondrocytes isolated from 16 patients undergoing total hip replacement because of OA (n=7) or due to a neck of femur fracture (NOF, n=9). ATAC-seq was similarly performed on bone-marrow mesenchymal stem cells (BM-MSC) and differentiated chondrocytes of two donors. DNA sequence reads (av. 50 million/sample) were aligned to human genome Hg38. Peaks were called using MACS2 and differential accessibility identified by DiffBind. Interexperiment comparisons and intersection with published gene expression changes, chondrogenesis ChIP-seq, knee ATAC-seq and human tissue scATAC-seq were performed in Galaxy and R. OA GWAS signal regions were overlapped with our defined chondrocyte ATAC-seq peaks. Results In BM-MSC and derived chondrocytes we mapped 138005 open chromatin regions, of which 20979 and 50699 significantly increased and decreased respectively during cell differentiation. In hip chondrocytes we identified 115295 open chromatin regions, 1383 and 573 were more or less differentially accessible respectively when comparing OA with NOF samples. In both data sets ‘newly accessible regions were enriched at enhancer regions (defined by ChIP-seq). Comparing the data with the ATAC-seq from the single cell ATLAS we identified 11866 open regions exclusive to chondrocytes. Genes associated with these regions were significantly enriched for cartilage-related gene ontology terms. Taking the 420 OA GWAS signals present in the GWAS catalogue, 313 of the OA regions (defined as lead SNP + proxy SNPs with r2 ≥ 0.8) overlapped with a chondrocyte ATAC-seq region. Conclusions Here we have mapped chromatin accessible region changes during chondrogenesis, showing that newly accessible regions are enriched at enhancer regions and positively correlate with gene expression. Open chromatin region changes between OA and NOF cartilage were fewer, and peak differences were subtle. Overall, we have associated OA GWAS loci with accessible regions and defined regions of the genome specific to cartilage and chondrogenesis.
Published in
Chromatin accessibility in MSC chondrogenesis, adult hip cartilage chondrocytes and osteoarthritis
Barter MJ, Soul J, Cheung K et al. · Osteoarthritis and cartilage 2026 · PMID 41512915 · doi:10.1016/j.joca.2025.12.015
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Direct links to NCBI, no account and no request form: the whole study as GSE270602_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 26 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1127542 and SRA study SRP515828. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
NOF, Patient ×9 OA, Patient ×7 MSC 2454E, Day0, ×3 MSC 2454E, Day14, ×3 MSC 8A, Day0, ×2 MSC 8A, Day14, ×2

Supports a between-group comparison across 26 samples.

6 replicated groups read from 26 sample titles; they account for 26 of them. Check it against the sample list below before relying on it.

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