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A high-risk osteoarthritis mutation in COL6A3 alters the mechanobiologic response of chondrocytes derived from human induced pluripotent stem cells

GSE293777 Homo sapiens (human) RNA-seq (gene expression) 84 samples Submitted 2025/04/08 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 84 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
84 samples: 14 conditions, mostly with about 6 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Osteoarthritis (OA) is a complex disease arising from a combination of genetic, biological, and mechanical risk factors that act, in part, to alter chondrocyte homeostasis. Our recent exome sequencing studies identified a causal OA variant in COL6A3, a monomeric unit of collagen type VI that serves as a distinguishing component of the pericellular matrix (PCM), a key transducer of mechanical and biochemical signals for the chondrocyte.
Read the full summary ↓
To study the effect of this mutation, human induced pluripotent stem cell (hiPSC)-derived chondrocytes, genetically edited to harbor the COL6A3 mutation, were used as an in vitro model to investigate chondrocyte mechanobiology and pathobiology. COL6A3 mutant chondrocytes exhibited reduced expression of key matrix proteins, suggesting altered PCM structure and composition. Functional analyses revealed altered mechanotransduction, characterized by heightened osmotically induced calcium signaling and reduced anabolic response to TRPV4 activation, at the transcriptional level and in matrix biosynthesis. RNA sequencing identified dysregulated pathways and aberrant TRPV4 signaling in mutant chondrocytes following mechanical loading. The presence of the COL6A3 mutation resulted in disrupted circadian rhythms, with increased BMAL1 expression and a significant phase shift, suggesting a link between the PCM and the circadian clock. Finally, COL6A3 mutant chondrocytes exhibited exacerbated catabolic response to interleukin-1, a key inflammatory cytokine in OA. Our study demonstrates the utility of a human iPSC-based system for studying the pathophysiology of specific OA risk alleles. These findings highlight the impact of the COL6A3 variant on chondrocyte physiology and support targeting mechanotransduction signaling pathways as a potential strategy for OA intervention in this case.
This dataset
Open GSE293777 in finder → Find more human RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE293777_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1246206 and SRA study SRP576389. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
14 conditions, mostly with about 6 replicates each
Wildtype, free-swelling, sample ×7 Wildtype, free-swelling +GSK205, sample ×7 Wildtype, loaded 0 hours, sample ×7 Wildtype, loaded 3 hours, sample ×7 Wildtype, loaded 3 hours + GSK205, sample ×7 Wildtype, loaded 0 hours + GSK205, sample ×6 Mutant, free-swelling, sample ×6 Mutant, free-swelling + GSK205, sample ×6 +6 more

Supports a case/control comparison: 39 samples read as cases, 45 as controls.

How we read this: 14 replicated groups read from 84 sample titles; they account for 84 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 44 more — browse all 84 samples with per-sample file links →

Datasets on a similar topic

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