Omics · study · 2026
3D Culture Reverses Limbal Niche Cell Replicative Aging via FOSL1 Upregulation
Listed in NCBI GEO
Limbal niche cells (LNCs) serve as essential regulators of limbal microenvironmental homeostasis and corneal epithelial wound repair, representing a promising therapeutic resource for limbal stem cell deficiency (LSCD).
Description
However, their clinical application is constrained by replicative aging during in vitro expansion. In this study, we investigated whether a three-dimensional (3D) Matrigel-based culture system could modulate replicative aging in LNCs.
Compared with conventional two-dimensional (2D) culture, 3D-cultured LNCs restored stemness marker expression and enhanced proliferative capacity. Concurrently, these cells displayed reduced senescence-associated β-galactosidase (SA-β-gal) activity and decreased expression of senescence-associated proteins, including p16, p21, p53, and γ-H2AX. Single-cell RNA sequencing (scRNA-seq) analysis revealed prominent upregulation of FOS-like antigen 1 (FOSL1).
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FOSL1 is a component of the AP-1 transcription factor family and participates in cell proliferation and stress adaptation. Functional assays using an in vitro replicative aging model showed that FOSL1 knockdown in early-passage (P4) LNCs accelerated senescence, whereas FOSL1 overexpression in late-passage (P11) LNCs attenuated senescence. Mechanistically, FOSL1 knockdown induced mitochondrial dysfunction characterized by elevated levels of mitochondrial superoxide and cellular reactive oxygen species (ROS), as well as a decreased in mitochondrial membrane potential, while FOSL1 overexpression preserved mitochondrial integrity and function.
Collectively, our findings demonstrate that 3D culture reverses LNC replicative aging through FOSL1-mediated enhancement of mitochondrial function, providing a microenvironment-based strategy to counteract replicative aging in adult stem cells for corneal regenerative therapy.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE343nnn/GSE343251 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE343251 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1510297 ncbi.nlm.nih.gov/bioproject/PRJNA1510297 ↗
project · from NCBI GEO
- PubMed 42712045 pubmed.ncbi.nlm.nih.gov/42712045 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE343251 | 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |