Omics · study · 2026
PAX3-SIX2 muscle stem cell heterogeneity drives muscle-specific repair dynamics diversification
Listed in NCBI GEO
The human body contains around 640 distinct muscles, each capable of regeneration following injury through the action of muscle-specific stem cells (MuSCs) that express the transcription factor PAX7.
Description
Its paralog, PAX3, a master regulator of embryonic myogenesis, is selectively expressed in a subset of adult quiescent MuSCs. The proportion of PAX3⁺ MuSCs varies across muscles.
By combining lineage tracing and skeletal muscle injury, we demonstrate that PAX3 drives MuSC diversity and muscle-specific regeneration rates. PAX3-expressing MuSCs display enhanced proliferation and differentiation capacities, enabling a faster response following injury, whereas loss of PAX3 leads to proliferation arrest and cell death. Single-cell RNA-sequencing analyses revealed the specific expression of Six2 in PAX3+ MuSCs.
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We show that PAX3 is required for SIX2 expression, and loss of SIX2 in MuSCs reduces proliferation and differentiation rates. Conversely, ectopic Six2 expression promotes a faster response in PAX3- MuSCs. With this work, we establish that PAX3/SIX2 expression correlates with distinct MuSCs behavior, influencing regeneration rates in a muscle-type-dependent context.
Our findings highlight a previously unrecognized layer of regulation in MuSCs behaviour and muscle repair and suggest that PAX3-SIX2 heterogeneity could be leveraged for targeted therapeutic strategies in muscle-wasting diseases.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302292 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302292 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1289821 ncbi.nlm.nih.gov/bioproject/PRJNA1289821 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Related
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE302292 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |