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NOTCH2 disrupts the synovial fibroblast identity and the inflammatory response of epiphyseal chondrocytes

GSE292806 Mus musculus (mouse) Single-cell RNA-seq 15 samples Submitted 2025/06/25 Platform GPL19057
At a glance

Single-cell RNA-seq · mouse · 15 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
15 samples: 4 × Notch2tm1.1Ecan Experimental chondrocytes, vs 4 × (Rosa26) Wild type chondrocytes, vs 4 × Rosa26NICD2 Experimental chondrocytes, vs 3 × (Notch2) Wild type chondrocytes,Groups 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.
Paper
NOTCH2 disrupts the synovial fibroblast identity and the inflammatory response of epiphyseal chondrocytesThe Journal of biological chemistry · 2025
Summary (written by the submitters)
Notch signaling plays a fundamental role in the inflammatory response and has been linked to the pathogenesis of osteoarthritis in murine models of the disease and in humans, but the mechanisms are poorly understood. We examined the effects of NOTCH2 in chondrocytes from Notch2tm1.1Ecan mice harboring a NOTCH2 gain-of-function mutation and from R26-NICD2 mice, a conditional gain-of-NOTCH2 function model, expressing the NOTCH2 intracellular domain (NICD2) from the Rosa26 locus.
Read the full summary ↓
Bulk RNA-Sequencing (Seq) revealed increased expression of pathways associated with the phagosome, the role of osteoclasts in rheumatoid arthritis signaling and pulmonary fibrosis signaling in Notch2tm1.1Ecan and NICD2-expressing cultures. Collagen degradation was enhanced in Notch2tm1.1Ecan chondrocytes and the osteoarthritis pathway in NICD2-expressing cells. Single cell (sc)RNA-Seq analyzed 7,845 control and 7,141 Notch2tm1.1Ecan cells and used to define cell clusters. The more prevalent ones were constituted by limb mesenchyme, chondrogenic cells and fibroblasts including articular synovial fibroblasts. Pseudotime trajectory finding revealed a good association among clusters in control cultures, but this was disrupted in the articular/synovial cluster from Notch2tm1.1Ecan mice. scRNA-Seq of R26-NICD2 mice analyzed 9,957 cells in control and 9,924 in NICD2-expressing cultures. Neither the cluster distribution nor the pseudotime trajectory analysis revealed substantial differences between NIDC2-expressing and control cells except for an altered progression in an undefined cluster in NICD2-expressing cells. In conclusion, NOTCH2 enhances the activity of pathways associated with inflammation in epiphyseal chondrocytes and disrupts the transcriptome profile of articular/synovial fibroblasts.
Published in
NOTCH2 disrupts the synovial fibroblast identity and the inflammatory response of epiphyseal chondrocytes
Canalis E, Guzzo R, Schilling L et al. · The Journal of biological chemistry 2025 · PMID 40345585 · doi:10.1016/j.jbc.2025.110206
This dataset
Open GSE292806 in finder → Find more mouse 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 GSE292806_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1241286 and SRA study SRP572758. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40345585) ↗
Study design
4 × Notch2tm1.1Ecan Experimental chondrocytes, vs 4 × (Rosa26) Wild type chondrocytes, vs 4 × Rosa26NICD2 Experimental chondrocytes, vs 3 × (Notch2) Wild type chondrocytes,

Supports a between-group comparison across 15 samples.

How we read this: 4 replicated groups read from 15 sample titles; they account for 15 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
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