Omics · study · 2026
Secreted Protein Combination GAPDH/S100A8/S100A9 from Human Expanded Potential Stem Cells Counteracts Mesenchymal Stem Cell Senescence
Listed in NCBI GEO
Human mesenchymal stem cells (hMSCs) remain the most clinically advanced adult stem cell source; however, their therapeutic potential is limited by rapid replicative senescence during ex vivo expansion.
Description
Replicative senescence in hMSCs is characterized by cell cycle arrest, acquisition of senescence-associated β-galactosidase (SA-β-Gal) activity, and secretion of the senescence-associated secretory phenotype (SASP) factors.
We investigated whether conditioned medium derived from human extended pluripotent stem cells (hEPSCs), which possess both embryonic and extra-embryonic developmental potential beyond that of conventional hESCs, could attenuate replicative senescence in hMSCs. Using sequential ultrafiltration (10 kDa and 3 kDa) followed by LC-MS/MS, we identified several proteins from hEPSC-conditioned medium. We then tested the combination of S100A9/GAPDH/S100A8 proteins for their effects on doxorubicin-induced and replicative senescence.hEPSC-conditioned medium markedly attenuated replicative senescence in hMSCs.
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Notably, the combination of S100A9/GAPDH/S100A8 proteins not only mitigated doxorubicin-induced senescence but also counteracted replicative senescence, as evidenced by a significant reduction in SA-β-Gal-positive cells and downregulated mRNA expression of senescence-associated genes, including p16, p21, and the SASP factor IL-6. Furthermore, EdU incorporation assays revealed significantly enhanced proliferative capacity following treatment.
Collectively, our findings establish a defined protein combination (S100A9/GAPDH/S100A8) that counteracts both replicative and stress-induced senescence, offering a novel, cell-free strategy to enhance the clinical utility of hMSCs.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326160 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326160 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1444037 ncbi.nlm.nih.gov/bioproject/PRJNA1444037 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Mass spectrometry 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE326160 | 12 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[modality].local:modality:mass-spectrometry | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:9606 | 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 |