Omics · study · 2026
PTEN, a master driver of nonhealing phenotype in venous leg ulcers, suppresses immune response, angiogenesis and lymphangiogenesis [scRNA]
Listed in NCBI GEO
We used single-cell RNA-Seq (scRNA-Seq) and bulk RNA-Seq to identify molecular mechanisms and cellular functions associated with impaired healing in venous leg ulcer (VLU). scRNA-Seq of chronic VLUs revealed impairments in immune, lymph endothelial, and endothelial cells, along with the underlying signaling pathways.
Description
Next, patients were treated with the standard of care and wound healing was followed for at least 4 weeks to distinguish healing and non-healing VLU.
RNA-Seq was performed on healing and non-healing VLUs, and transcriptomes were compared to those of human acute wounds (AW). A robust suppression of inflammatory response, lymphangiogenesis and angiogenesis was hallmark of non-healing, in contrast to healing VLUs that showed similarity to physiological healing. Diminished inflammatory response in non-healing VLUs was due to impaired leukocyte transmigration and egression, with suppression of kinases’ activity, including AKT, ERK, JNK1/2, SRC, and PDGFR, underlining the non-healing signature.
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Bioinformatic analyses pinpointed PTEN as a master negative regulator of the processes and signaling pathways suppressed in non-healing VLU. Indeed, increased PTEN was confirmed in non-healing compared to healing VLUs on scRNA-Seq and protein level. Functional in vivo murine studies confirmed that pharmacological PTEN inhibition enhances immune response, and proinflammatory signals, leading to accelerated wound closure.
We identify PTEN as a master regulator of non-healing VLU phenotype that orchestrates multiple key processes responsible for impaired healing. Targeting PTEN as a therapeutic approach may shift non-healing VLUs into healing trajectory allowing for progression of wound closure.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE282nnn/GSE282418 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282418 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1188556 ncbi.nlm.nih.gov/bioproject/PRJNA1188556 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 65% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE282418 | 15 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 (65%) |
| concepts[modality].local:modality:single-cell-rna-seq | 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 |